Altered Mental Status in an Elderly Woman with Concurrent Takotsubo Syndrome and Polymyalgia Rheumatica: A Case of Treatable Geriatric Delirium
Hien Nguyen, MD; Connie Le, MD; Hanh Nguyen, MD; Nam-Tran Nguyen
Winter 2012 - Volume 16 Number 1
We present a unique case of a patient, aged 80 years, who presented with delirium and takotsubo syndrome. Also known as “broken heart syndrome” because it often originates following an emotional stress, takotsubo syndrome may be difficult to distinguish from myocardial infarction because of similar symptoms and demographics. However, the distinction of these opposing diagnoses is significant because takotsubo syndrome is associated with more favorable prognosis for complete recovery, especially with early diagnosis and expedient supportive therapy. To our knowledge, we present the first case of takotsubo syndrome in which the diagnosis was made in an elderly patient presenting with delirium and in the absence of the hallmark symptoms of chest pain and dyspnea. Finally, we describe this patient’s coexistent diagnosis of polymyalgia rheumatica and speculate on its possible theoretic relationship to takotsubo syndrome.
Takotsubo syndrome has historically been considered quite rare but currently is suspected to be underdiagnosed, because the estimated incidence is approximately 1.7% to 2.2% of patients presenting with acute myocardial infarction (MI).1,2 It is important that physicians be familiar with this diagnosis because the elderly are rapidly becoming a large segment of the population. An enigmatic condition first described in 1990, takotsubo syndrome has the cardinal symptoms of angina and dyspnea, mimicking acute coronary syndrome.1,2 We present a case of rapidly reversible delirium heralded by the diagnosis of concurrent takotsubo syndrome and polymyalgia rheumatica (PMR).
A black woman, age 80 years, with type 2 diabetes and hypertension was admitted to the hospital because of an acute change in sensorium evolving over two days, with abrupt aberrant sleep-wake cycles (agitated and awake at nighttime; sleeping in the daytime), fluctuating disorientation to family members, and refusal of food. At admission, it was found that her medications included mirtazapine, lisinopril, metformin, atenolol, simvastatin, and aspirin. A full review of organ systems revealed a five-pound weight loss, fatigue, myalgias, and low-grade fevers over the preceding month. The patient reported no chest pains, shortness of breath, headaches, abdominal pains, or falls at any time period before or during her acute decompensation. However, later during her hospital stay, a family member reported that the patient’s sister had recently died.
At admission, she was febrile, with a temperature of 100.3°F, and this continued intermittently throughout her hospitalization. Examination showed her blood pressure to be 73/49 mm Hg, her pulse to be 90 beats/minute, and her respiratory rate to be 22 breaths/minute. She had leukocytosis (30,000 cells/mm3), mild acute renal insufficiency (creatinine of 1.8 mg/dL), normal acid-base values, and slightly elevated liver enzyme levels. Her erythrocyte sedimentation rate was elevated, at 91 mm/h, and her C-reactive protein level was elevated, at 153 mg/L. Findings were normal on flow cytometry studies and on tests to evaluate for connective-tissue diseases, including antinuclear antibody, rheumatoid factor, anti-SSA, anti-SSB, cytoplasmic antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibodies, hepatitis, cryoglobulins, and anticardiolipin antibody. Findings on blood cultures for infectious etiologies and on tests for mononucleosis, lyme disease, thyroid disease, syphilis, human immunodeficiency virus, tuberculosis, and Clostridium difficile infection were all normal. Neither whole-body computed tomography (CT) scanning of the chest, abdomen, and pelvis nor positron-emission tomography, indium white-blood-cell scanning, or gallium scanning revealed occult infection or malignancy.
An initial electrocardiogram revealed new acute deep T-wave inversions in all precordial leads, along with an old right bundle-branch block (Figures 1 and 2). Initial creatine kinase MB fractions and troponin levels were normal, as were follow-up serial cardiac enzyme levels. An initial echocardiogram demonstrated mild concentric left ventricular hypertrophy with a severely depressed ejection fraction of 20% and prominent apical ballooning (Figure 3). Complete restoration of cardiac ejection fraction was confirmed by echocardiography one week later (Figure 4). Cardiac CT scans demonstrated normal coronary vasculature, other than minimal coronary calcifications. Findings on a nuclear stress test were normal, with an ejection fraction of 58%. Thus, the consulting cardiologist recommended medical management. Initially, cardiac catheterization was contemplated, but it was not completed because cardiac function was rapidly reversible and because of benign findings on noninvasive evaluations. In the interim, the patient was treated with standard supportive therapy, including oxygen, acetylsalicylic acid, and intravenous hydration for hypotension.
Once infectious etiologies were excluded, a rheumatology consultant initiated corticosteroidal therapy at a dose of 20 mg of prednisone daily because of concern about the possibility of PMR, which was based on the patient’s clinical presentation and strikingly elevated levels of markers for inflammation. The patient’s cognition, laboratory-test findings, and functional status improved rapidly within less than one week, so she was transferred to subacute care with indefinite continuation of the prednisone dosage.
To the best of our knowledge, the case we present here is the first reported case of takotsubo syndrome in which delirium, in the absence of chest pain and shortness of breath, was the primary and unexpected manifestation. Our findings are in contrast with those of Malone et al,3 who reported that delirium may be the initial presentation for MI, the closest correlate of takotsubo syndrome. In that study of very old patients with acute MI, delirium developed in 28%; delirium was only rarely the initial presentation for MI.
Delirium involves acute global changes in cognition and consciousness. Its causes can be placed into four broad categories: metabolic, toxic, structural, and infectious.4 An alternative classification scheme is medical, chemical, surgical, or neurologic.4 However, delirium often has multiple causes, as was the situation with our patient, who had multiple preexisting medical comorbidities and presented with multisystemic disease. We believe that her delirium was primarily caused by metabolic derangements (hypotension, renal insufficiency, and transient heart failure). A frequent iatrogenic cause of delirium in the elderly is overmedication with, for example, tricyclic antidepressants and antiparkinsonian drugs. Elderly persons are especially at risk for delirium because of preexisting cognitive impairment, medical and psychiatric comorbidities, functional impairments, and polypharmacy.3,4
A diagnosis of takotsubo syndrome is based on four criteria developed by the Mayo Clinic: transient hypokinesis or akinesis of the left ventricle, sparing the apex; exclusion of obstructive coronary disease; electrocardiographic changes, including ST segment or T-wave inversions, and/or mild cardiac enzyme elevations; and exclusion of pheochromocytoma or myocarditis. The syndrome is sometimes called “broken heart syndrome” because of its high correlation with a stressful life event. Diagnosis is important because cardiogenic shock, pulmonary edema, dysrhythmia, left ventricular thrombus or free wall rupture, and death (mortality, 1.7%–2.3%). Takotsubo syndrome is also known as the broken heart syndrome because a stressful emotional stressor is often the trigger for the disease.5
In spite of the well-defined symptomatology of takotsubo syndrome, its diagnosis may be challenging because of ethnicity-, age-, and sex-related differences in presentations. Although 90% involve postmenopausal women older than 67 years, occurrences have been described in persons ranging in age from 2 to 80 years. In a recent case series in the US, 57% of patients were Asian, 40% were white, and 3% were of other ethinicity.1,2,5-7
Recently, Pezzo et al reported6 that blacks may present with dyspnea and without chest pain; our patient presented atypically with delirium and without angina or dyspnea. Other atypical presentations for takotsubo syndrome described in other case series include seizures, epigastric pain, or nausea and vomiting, but these patients also had concurrent chest pain and dyspnea.6
Therapy for takotsubo cardiomyopathy is generally supportive but may include aggressive treatment such as the use of inotropic agents or an intra-aortic balloon pump if there is severe or refractory hypotension. In most patients, the left ventricular ejection fraction normalizes within two months.6
PMR is characterized by fever, weight loss, fatigue, depression, proximal muscle pain and stiffness, and gel phenomenon and is seen more commonly in women older than age 50 years.8 Our patient’s elevated levels of inflammation markers and systemic symptoms strongly suggested a diagnosis of PMR concurrent with takotsubo syndrome, an association not previously reported.8 The diagnosis of PMR was strengthened when corticosteroids rapidly resolved her cognitive difficulties and aberrations on laboratory findings.
We speculate that there may be an association between takotsubo syndrome and PMR in the presence of a sympathetic nervous system dysfunction; this relationship is not unprecedented. There are two case reports in the medical literature describing reflex sympathetic dystrophy syndrome coexisting with PMR.9,10 Indeed, the most preeminent theory for the pathogenesis of takotsubo syndrome is a sympathetic hyperactivity, such as may occur from acute emotional or physical stress.9,10 However, it is entirely possible that the development of concurrent takotsubo syndrome and PMR was simply coincidental in this elderly patient, whose age group is associated with a higher incidence of both medical conditions independently.
A review of the literature illustrates two distinct cases of takotsubo syndrome associated with other acute conditions in which corticosteroids were interestingly prominent in the resolution of this cardiomyopathy, such as is illustrated in our case. Ukita et al reported resolution of takotsubo syndrome after corticosteroid therapy; the syndrome had developed during an acute adrenal crisis because of isolated adrenocorticotropin deficiency.11 Radhakrishnan and Granato reported resolution of this cardiomyopathy after corticosteroid therapy; it had developed during thyroid storm.12
PMR has not been previously described with delirium to our knowledge, and it is most closely related to temporal arteritis. Pascuzzi et al reported that a patient with temporal arteritis had a primary presentation of delirium—delusional thinking without concomitant headache or visual loss.13 We acknowledge, though, that our patient presented with other metabolic impairments that we believe contributed strongly to the development of delirium.
We presented the case of a patient with rapidly reversible delirium heralded by concurrent takotsubo syndrome and PMR. Both conditions are uncommon in general and even rarer when diagnosed concurrently in a single patient. Furthermore, our patient is black, a group that is not typically considered prone to PMR. Scandinavian people have been reported to have the highest rate of PMR, whereas black and Hispanic groups have the lowest rates.14 Less than 2% of patients diagnosed with takotsubo syndrome are black, with the majority being of Asian descent.7
Our case demonstrates valuable teaching points in the challenging management of delirium in an elderly patient. Delirium can have multiple etiologies, and atypical presentations for common medical conditions are commonplace in elderly patients presenting with delirium. Further research may be useful in searching for a possible relationship, based on sympathetic dysfunction, between takotsubo syndrome and PMR. This research will likely be facilitated by the rapid acceleration in the world’s geriatric population and an accompanying increase in the incidence of both of these medical conditions.
The author(s) have no conflicts of interest to disclose.
Katharine O’Moore-Klopf, ELS, of KOK Edit provided editorial assistance.
1. Satoh H, Tateishi H, Uchia T, et al. Stunned myocardium with specific (tsubo-type left ventriculographic configuration due to multivessel spasm. In: Kodama K, Haze K, Hori M, editors. Clinical aspects of myocardial injury: from ischemia to heart failure [In Japanese]. Tokyo: Kagakuhyouronsha; 1990. p 56–64.
2. Bybee KA, Prasad A, Barsness GW, et al. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol 2004 Aug 1;94(3):343–6.
3. Malone ML, Rosen LB, Goodwin JS. Complications of acute myocardial infarction in patients > or = 90 years of age. Am J Cardiol 1998 Mar 1;81(15):638–41.
4. Saxena S, Lawley D. Delirium in the elderly: a clinical review. Postgrad Med J 2009 Aug;85(1006):405–13.
5. Kawai S, Kitabatake R, Tomoike H; Takotsubo Cardiomyopathy Group. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circ J 2007 Jun;71(6):990–2.
6. Pezzo SP, Hartlage G, Edwards CM. Takotsubo cardiomyopathy presenting with dyspnea. J Hosp Med 2009 Mar;4(3):200–2.
7. Jabara R, Gadesam R, Pendyala L, Chronos N, King SB, Chen JP. Comparison of the clinical characteristics of apical and non-apical variants of “broken heart” (takotsubo) syndrome in the United States. J Invasive Cardiol 2009 May;21(5):216–22.
8. Subrahmanyan P, Dasgupta B. Polymyalgia rheumatica and giant cell arteritis. Br J Hosp Med (Lond) 2006 May;67(5):240–3. Erratum in: Br J Hosp Med (Lond) 2006 Jul;67(7):383.
9. Wysenbeek AJ, Calabrese LH, Scherbel AL. Reflex sympathetic dystrophy syndrome complicating polymyalgia rheumatica. Arthritis Rheum 1981 Jun;24(6):863–4.
10. Bordin G, Azteni F, Betatazzi L, Beyene NB, Carrabba M, Sarzi-Puttini P. Unilateral polymyalgia rheumatica with contralateral sympathetic dystrophy syndrome. A case of asymmetrical involvement due to pre-existing peripheral palsy. Rheumatology (Oxford) 2006 Dec;45(12):1578–80.
11. Ukita C, Mivazaki H, Tovoda N, Kosaki A, Nishikawa M, Iwasaka T. Takotsubo cardiomyopathy during acute adrenal crisis due to isolated adrenocorticotropin deficiency. Intern Med 2009;48(5):347–52.
12. Radhakrishnan A, Granato JE. An association between Takotsubo cardiomyopathy and thyroid storm. Postgrad Med 2009 May;121(3):126–30.
13. Pascuzzi RM, Roos KL, Davis TE Jr. Mental status abnormalities in temporal arteritis: a treatable cause of dementia in the elderly. Arthritis Rheum 1989 Oct;32(10):1308–11.
14. Labbe P, Hardouin P. Epidemiology and optimal management of polymyalgia rheumatica. Drugs Aging 1998 Aug;13(2):109–18.
More from this Journal section
Echinococcus of the Liver Treated with Laparoscopic Hepatectomy
Thursday, 27 May 2010
Erina N Foster, MD; Gabor Hertz, MD Summer 2010 - Volume 14 Number 2 Abstract Echinococcosis or hydatid disease is endemic to many countries around the world where livestock, mainly sheep and cattle, are raised with dogs who act as the definitive hosts for the adult phase of the echinococcal tapeworm. We report a case of a man, age 22 years, who emigrated from Kyrgyzstan as a teenager, presenting with abdominal fullness and nausea and found to have a 9 cm echinococcal cyst of the liver which was successfully treated with laparoscopic hepatectomy because of a very favorable location. Case Presentation We report a case of a man, age 22 years, from Kyrgyzstan who presented with abdominal fullness and nausea. An ultrasound was performed and revealed a complex cystic liver mass. Computed tomography (CT) showed a large, mixed-density mass in the left lobe approximately 9 cm in size, with nondependent hypodense foci (Figure 1). His mother had mentioned another villager was diagnosed with a similar problem and was treated with surgery. Laboratory evaluation revealed no leukocytosis, normal blood count and liver enzymes. Echinococcal antibody was mildly elevated at 1.32 (positive over 1.2) and he was placed on albendazole 400mg bid preoperatively. Because of the advantageous location of the cystic mass, the patient was able to undergo laparoscopic segmental hepatectomy 4 weeks later (Figures 2 and 3). No postoperative complications were noted and the patient continued to do well 2 months after surgery. Discussion Echinococcosis or hydatid disease is endemic in the Mediterranean, Africa, Middle East, South America, Australia, Russia, and China where livestock, mainly sheep and cattle, are raised with dogs who act as the definitive hosts for the adult phase of the echinococcal tapeworm. Kyrgyzstan is a small, landlocked central Asian country, bordered by China, Kazakhstan, Uzbekistan, and Tajikistan with an estimated population of 5.4 million people. Kyrgyzstan has a predominantly agricultural economy, producing cotton, tobacco, wool, and meat.1 Livestock become infected when they eat food or water contaminated with dog feces which contain the larval form of the tapeworm. Infection leads to cysts in the liver in 75% of cases followed by lung, but can involve any part of the body.2 Mortality is estimated at 5% and sensitization can occur with systemic leakage of cysts into the bloodstream potentially leading to fatal anaphylaxis if a cyst ruptures.3 Most infections are caused by Echinococcus granulosus followed by Echinococcus multilocularis.3 Laboratory examination can rarely show a peripheral eosinophilia but usually the complete blood count is normal. Serologic testing is 84% sensitive but cannot definitively rule the diagnosis in or out.3 Imaging with ultrasound can show single or multiloculated cysts with a “snowflake or hail-storm” pattern and signs on CT include daughter cysts with a “wheel, rosette, or honeycomb-like” appearance.4 Treatment varies depending on the location, size of the cyst, and overall health of the patient. Surgical resection has been the treatment of choice but newer modalities through percutaneous aspiration called PAIR (puncture, aspiration, injection, and re-aspiration of scolicidal solutions) show promise. Patients treated with PAIR usually receive oral medication (albendazole or mebendazole) for 7 days before and 28 days after aspiration to help decrease the risk of recurrence.5 Surgical options include total pericystectomy, partial hepatectomy, and lobectomy, and can be complicated by bleeding, bile leak from the residual cavity, biliary fistula, or cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) is employed to mainly assist in postoperative management of these complications. Fortunately, the location of the cyst in our patient made it feasible to perform minimally invasive laparoscopic resection of his lesion. Disclosure Statement The author(s) have no conflicts of interest to disclose. References 1. The World Factbook: Central Asia: Kyrgyzstan [monograph on the Internet]. Washington, DC: Central Intelligence Agency; updated biweekly [cited 2010 Feb 1]. Available from: www.cia.gov/library/publications/the-world-factbook/geos/kg.html#. 2. Voros D, Katsarelias D, Polymeneas G, et al. Treatment of hydatid liver disease. Surg Infect (Larchmt) 2007 Dec;8(6):621-7. 3. Chrieki M. Echinococcosis–an emerging parasite in the immigrant population. Am Fam Physician 2002 Sep 1;66(5):817-20. 4. Czermak BV, Akhan O, Hiemetzberger R, et al. Echinococcosis of the liver. Abdom Imaging 2008 Mar-Apr;33(2):133-43. 5. Smego RA Jr, Sebanego P. Treatment options for hepatic cystic echinococcosis. Int J Infec Dis 2005 Mar;9(2):69-76.
Late-Presenting Complications After Splenic Trauma
Thursday, 27 May 2010
Sandra Freiwald, MD, FACS Summer 2010 - Volume 14 Number 2 Abstract Since the 1970s, the management of blunt splenic trauma has evolved from almost exclusive surgical management to selective use of nonsurgical management in hemodynamically stable patients. Understanding of the spleen’s immunologic importance in protection against overwhelming postsplenectomy infection led to development first of surgical techniques for splenic salvage and later to protocols for nonsurgical management of adults with blunt splenic injury. The evolution of nonsurgical management has resulted in new patterns of postsplenic trauma complications. This article describes a pancreatic pseudocyst, one of several described delayed complications of nonsurgical management of blunt splenic trauma. Along with missed splenic injury and delayed rupture, the development of a splenic pseudocyst represents challenges for any multidisciplinary team involved in trauma care. Detection and management of these complications is discussed, as is postsplenectomy vaccination and return to activity. Case Presentation A man, age 19 years, presented to his Primary Care physician with left upper quadrant pain. One month earlier, he had been found to have infectious mononucleosis. Outpatient abdominal ultrasonography revealed splenomegaly with contour irregularity of the spleen. Computed tomography (CT) demonstrated a very large splenic pseudocyst (Figure 1). He was referred to general surgery for further treatment. The patient was a high school athlete who had been recruited to attend a prominent university on a sports scholarship. He was scheduled to begin training approximately five months after presenting to the general surgery clinic. He requested an intervention that might allow him to return to sports as quickly as possible. After consultation with an attending trauma surgeon at a local trauma center, plans were made for Interventional Radiology to aspirate the pseudocyst. A clinician easily removed 1500 mL of old blood, and only a small residual fluid collection remained after the procedure. One month later, follow-up CT demonstrated reaccumulation of the fluid. This time, an indwelling drain was placed by Interventional Radiology. Over the next month, the fluid collection resolved and the drain was removed. One month later, the patient reported increasing left upper quadrant pain. Repeat CT demonstrated recurrence of the fluid collection. It was again percutaneously drained, this time augmented by the use of tissue plasminogen activator administered through the drain. Another month passed, the fluid collection resolved, and the spleen appeared normal on CT. The drain was removed. The patient did well for one month. He attended training camp after the team physician was contacted and fully apprised of the patient’s recent medical history. Unfortunately, the patient became febrile. Laparoscopic splenectomy was attempted and was unsuccessful. He therefore underwent open splenectomy and recovered uneventfully. Discussion This case represents one of several delayed complications of blunt splenic injury encountered by our general surgery team. Along with missed splenic injury and delayed rupture, the development of a splenic pseudocyst represents challenges for any multidisciplinary team involved in trauma care. Since the 1970s, the treatment of blunt splenic trauma has evolved from almost exclusively surgical to selective use of nonsurgical treatment in hemodynamically stable patients. Understanding of the immunologic importance of the spleen and its role in protection against overwhelming postsplenectomy infection (OPSI) led to development first of surgical techniques for splenic salvage and later to protocols for nonsurgical treatment of adults with splenic injury. Presently, >60% of adults with splenic injury are successfully treated without surgery.1 The evolution of surgical treatment has resulted in new patterns of postsplenic trauma complications. Missed Splenic Injury Missed splenic injury is the most common cause of preventable death after blunt abdominal trauma.2 Compared with patients in whom injury is promptly recognized, those with delay in diagnosis of splenic trauma have a ten-fold increase in mortality.3 It is therefore important to have a high index of suspicion for this diagnosis when evaluating patients with blunt trauma. The most common finding associated with splenic rupture is left lower rib fractures, which occur in >40% of cases. When such fractures are present, further assessment with abdominal and pelvic CT is required. The classic triad associated with blunt splenic rupture—left hemidiaphragm elevation, left lower lobe atelectasis, and left pleural effusion—is frequently absent and cannot be considered a reliable indicator. Any patient who does have left hemidiaphragm elevation after blunt trauma should be considered to have a splenic injury until it is proven otherwise. Once the diagnosis is made, treatment depends on the hemodynamic condition of the patient. Unstable patients require emergency splenectomy, whereas those in stable condition can undergo nonoperative management. Delayed Rupture of the Spleen Delayed splenic rupture was first described in 1902 by Baudet,4 who noted its occurrence 48 hours after trauma. The incidence is approximately 1%, and it tends to occur between 4 and 8 days after injury.5 Mortality ranges from 5% to 15%, compared with 1% mortality for acute injury.6 Potential mechanisms include expansion of a subcapsular hematoma, clot disruption, or rupture of a pseudoaneurysm or splenic pseudocyst. Prompt recognition of the signs and symptoms of delayed splenic rupture is essential. Patients typically exhibit hypotension, tachycardia, worsening abdominal pain and distension, and a decreasing hematocrit. The treatment of choice is splenectomy, as splenorrhaphy can be extremely difficult in patients in whom surgical treatment has failed. Some centers will perform angioembolization in hemodynamically stable patients. Splenic Pseudocyst The diagnosis of splenic pseudocyst is becoming more common, probably because of the increasing use of CT and ultrasonography to evaluate complaints of upper abdominal pain as well as the increased frequency of nonoperative treatment of blunt splenic trauma. Thirty percent to 60% of splenic pseudocysts are asymptomatic,7 causing problems only as they enlarge. Common presenting complaints include left upper quadrant pain and nausea and vomiting because of compression of the stomach. Diagnosis is made in the setting of a history of blunt abdominal trauma, upper abdominal pain, and a perisplenic cyst on abdominal imaging. The optimal treatment for splenic pseudocysts remains to be defined. Splenectomy was the traditional treatment of choice. With increasing recognition of the immunologic importance of the spleen, this fell from favor. A number of spleen-preserving techniques have been attempted, including watchful waiting, percutaneous drainage (as done in our case), marsupialization/fenestration, splenic decapsulation, and complete cystectomy with partial splenectomy. Marsupialization entails making an opening in the cyst wall to allow drainage to occur. Decapsulation requires near-total resection of the cyst while leaving the spleen intact with part of the cyst wall attached to the capsule. Small series have been reported in the investigation of various methods for treating splenic pseudocysts. Percutaneous drainage has had varying degrees of success, but most series have shown high recurrence rates, sometimes in 100% of patients. Laparoscopic fenestration has been successful in some cases, as has open decapsulation. One series of seven patients concluded that small cysts (<5 cm in diameter) were likely to resolve spontaneously, although this could take up to three years. Larger cysts in that series required some sort of intervention; percutaneous drainage failed in 10% of patients, necessitating cystectomy with splenectomy or splenorrhapy.8 In a more recent series of six patients, the failure rate for percutaneous drainage and laparoscopic fenestration was 100%. The authors believed that complete removal of the cyst, with partial or complete splenectomy, ought to be the procedure of choice in young, otherwise healthy patients with large symptomatic splenic pseudocysts.9 In retrospect, this probably would have been the best option for our patient, allowing quicker recovery and fewer invasive procedures. Overwhelming Postsplenectomy Infection OPSI, typically caused by the encapsulated organisms Streptococcus pneumonia, Haemophilus influenza, and Neisseria meningitidis, occurs in 0.05% to 2% of patients who have undergone splenectomy.10 It may develop immediately or as late as 65 years after splenectomy. Mortality is significant and as high as 50%.10–12 After splenectomy, reduced levels of immunoglobulin M, opsonins, and splenic tuftsin hamper the body’s ability to clear encapsulated bacteria. Vaccination to stimulate immunity against these organisms is commonly done despite the absence of strong data to support its efficacy. As concerns have been raised about the ability to generate an appropriate immune response in the perioperative period, especially in the critically ill, controversy exists regarding the optimal timing of vaccination. Two prospective randomized, controlled trials have shown that pneumococcal vaccine results in the highest antibody titer response when given 14 days after splenectomy.13,14 Prospective data support the vaccination of asplenic patients, on the basis of knowledge of the spleen’s role in protection against infection by encapsulated organisms.15 Need for revaccination has been established by prospective studies of antibody levels and efficacy after initial vaccination.11 There are no data from prospective randomized, controlled trials identifying appropriate timing for vaccination before elective splenectomy. Patients are typically vaccinated 2 weeks before surgery, but this practice is supported only by retrospective data.13,14 The Centers for Disease Control and Prevention (CDC) recommends that after splenectomy, all patients receive 23-valent pneumococcal vaccine (Pneumovax 23), meningococcal vaccine (Menactra for patients between the ages of 16 and 55 years and Menomune-A/C/Y/W-135 for those older than 55 years), and Haemophilus influenzae type b vaccine (HibTITER). Vaccination should take place two weeks before elective splenectomy or two weeks after emergency splenectomy. A booster dose of pneumococcal vaccine is recommended after five years. Patients who receive the meningococcal polysaccharide vaccine (Menomune A/C/Y/W-135) should be revaccinated every three to five years. Patients who receive the meningococcal polysaccharide diphtheria toxoid conjugate vaccine (Menactra) probably should be revaccinated every three to five years. Long-term studies regarding revaccination are ongoing, and the manufacturers suggest contacting them for their latest recommendation. The HibTITER vaccine does not require repeated administration. The recommendation to give the vaccines two weeks after emergency splenectomy must be tempered by the patient’s reliability. Many trauma centers give the vaccines immediately before the patient is discharged home in case the patient does not return for follow-up care. In addition to vaccination, all patients must be educated about the signs and symptoms of OPSI and must be instructed to seek immediate medical attention for febrile illness. Asplenic travelers are advised to contact the CDC before traveling abroad, to learn about increased risk of contracting meningococcal infections in sub-Saharan Africa, India, and Nepal. Return to Activity Another area of controversy in the treatment of patients after splenic trauma is timing of return to activity. Few data exist regarding activity guidelines after discharge from a hospital or trauma center. Traditionally, patients have been told to refrain from physical activity for three months after splenic injury.16 A survey of members of the Eastern Association for the Surgery of Trauma (EAST) was published documenting how members of this society treat their patients after blunt splenic trauma. In patients with grade I or grade II (Table 1)17 injury, the majority of respondents allowed resumption of light activity in two weeks and full activity in six weeks. These decisions were rarely based on repeat imaging with CT but were primarily based on clinical judgment. In patients with a higher grade of injury (III, IV, or V), half of respondents allowed their patients to return to light activity in four to six weeks. The other half waited two to three months. As for return to full activity, patients were told to wait for four to six months by 20% of surgeons when they had a grade III injury and by 30% of surgeons when they had a grade IV or grade V injury. Five percent of surgeons did not allow return to full activity for high-grade injuries for longer than six months.18 With higher-grade injuries, there was more reliance on CT findings after discharge in decision making, which is contrary to recommendations in the current literature.19 Pediatric trauma series have demonstrated more concrete evidence of timing for splenic injuries to heal. CT has documented that 90% of grade III injuries healed in 76 ± 7 days and that 77% of grade IV injuries healed within 81 ± 8 days.20 Although there are no studies proving that adult spleens heal at the same pace as those of children, those healing rates suggest that activity restriction for four to six months for adults may be excessive. As this issue can significantly affect quality of life in a typically young and otherwise healthy population, there is a need for a well-designed study to address it. Conclusion Delayed complications of blunt splenic trauma may be encountered in settings outside of trauma centers. Practitioners must be familiar with these issues and involve appropriate specialists as needed in the care of patients with splenic injury. Disclosure Statement The author(s) have no conflicts of interest to disclose. Acknowledgment Katharine O’Moore-Klopf, ELS, of KOK Edit provided editorial assistance. References 1. Cales RH, Trunkey DD. Preventable trauma deaths: A review of trauma care systems development. JAMA 1985 Aug 23–30;254(8):1059–63. 2. Berlatzky Y, Shiloni E, Anner H, Weiss Y. “Delayed rupture of the spleen” or delayed diagnosis of the splenic injury? Isr J Med Sci 1980 Sep–Oct;16(9–10):659–64. 3. Pachter HL, Guth AA, Hofstetter SR, Spencer FC. Changing patterns in the management of splenic trauma: the impact of nonoperative management. Ann Surg 1998 May;227(5):708–19. 4. Schwartz SI, editor-in-chief; Shires GT, Spencer FC, editors. Principles of Surgery. 5th edition. New York: McGraw-Hill; 1989. 5. Cocanour CS, Moore FA, Ware DN, Marvin RG, Clark JM, Duke JH. Delayed complications of nonoperative management of adult splenic trauma. Arch Surg 1998 Jun;133(6):619–25. 6. Kluger Y, Paul DB, Raves JJ, et al. Delayed rupture of the spleen—myths, facts and their importance: case reports and literature review. J Trauma 1994 Apr;36(4):568–71. 7. Labruzzo C, Haritopoulos KN, El Tayar AR, Hakim NS. Posttraumatic cyst of the spleen: a case report and review of the literature. Int Surg 2002 Jul–Sep;87(3):152–6. 8. Pachter HL, Hofstetter HR, Elkowitz A, Harris L, Liang HG. Traumatic cysts of the spleen—the role of cystectomy and splenic preservation: experience with seven consecutive patients. J Trauma 1993 Sep;35(3):430–6. 9. Wu HM, Kortbeek JB. Management of splenic pseudocysts following trauma: a retrospective case series. Am J Surg 2006 May;191(5):631–4. 10. Shatz DV. Vaccination practices among North American trauma surgeons in splenectomy for trauma. J Trauma 2002 Nov;53(5):950–6. 11. Rutherford EJ, Livengood J, Higginbotham M, et al. Efficacy and safety of pneumococcal revaccination after splenectomy for trauma. J Trauma 1995 Sep;39(3):448–52. 12. Dickerman JD. Traumatic asplenia in adults: a defined hazard? Arch Surg 1981 Mar;116(3):361–3. 13. Shatz DV, Romero-Steiner S, Elie CM, Holder PF, Carlone GM. Antibody responses in postsplenectomy trauma patients receiving the 23-valent pneumococcal polysaccharide vaccine at 14 versus 28 days postoperatively. J Trauma 2002 Dec;53(6):1037–42. 14. Shatz DV, Schinsky MF, Pais LB, Romero-Steiner S, Kirton OC, Carlone GM. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy. J Trauma 1998 May;44(5):760–6. 15. Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbial Infect 2001 Dec;7(12):657–60. 16. Gandhi RR, Keller MS, Schwab CW, Stafford PW. Pediatric splenic injury: pathway to play? J Pediatr Surg 1999 Jan;34(1):55–9. 17. Moore EE, Cogbill TH, Jurkovich GJ, Shackford SR, Malangoni MA, Champion HR. Organ injury scaling: spleen and liver (1994 revision). J Trauma 1995 Mar;38(3):323-4. 18. Fata P, Robinson L, Fakhry SM. A survey of EAST member practices in blunt splenic injury: a description of current trends and opportunities for improvement. J Trauma 2005 Oct;59(4):836–42. 19. Uecker J, Pickett C, Dunn E. The role of follow-up radiographic studies in nonoperative management of spleen trauma. Am Surg. 2001 Jan;67(1):22–5. 20. Rovin JD, Alford BA, McIlhenny TJ, Burns RC, Rodgers BM, McGahren ED. Follow-up abdominal computed tomography after splenic trauma in children may not be necessary. Am Surg 2001 Feb;67(2):127–30.
The Treatment of Black Widow Spider Envenomation with Antivenin Latrodectus Mactans: A Case Series
Tuesday, 06 September 2011
Steven R Offerman, MD, FACEP, FACMT; G Patrick Daubert, MD, FACEP; Richard F Clark, MD, FACEP, FACMT Summer 2011 - Volume 15 Number 3 Abstract Black widow spiders (Latrodectus mactans) are found throughout the US. Though bites are relatively uncommon, they pose a significant health problem with over 2500 reported to American poison control centers annually. Black widow spider bites cause a characteristic envenomation syndrome consisting of severe pain, muscle cramping, abdominal pain, and back pain. The significant pain associated with envenomation is often refractory to traditional analgesics. Antivenom (Antivenin Latrodectus mactans) is available and effective, but is often withheld because of a fear of acute hypersensitivity reactions. We report four cases of symptomatic black widow spider envenomation. One of the reported cases was managed without antivenom, and, in contrast, three were treated successfully with Antivenin Latrodectus mactans. We believe that these cases demonstrate safe and effective use of black widow antivenom. This article presents the rationale for use of antivenom in these cases, and a nonsystematic review of the pertinent literature. Background Latrodectus species are found throughout the world. Five species of widow spiders occur in the US: the southern black widow (L mactans), the northern black widow (L variolus), the Western black widow (L hesperus), the brown widow (L geometricus), and the red widow (L bishopi). In North America, the most widely distributed native spider is L mactans, known as the black widow spider.1,2 Although most spiders produce venom, the vast majority lack mouthpieces (chelicerae) capable of delivering their venom through human skin.3–5 Black widow spiders are one of only a few spiders with the ability to cause a poisonous bite to humans.3,4 Only female widow spiders are dangerous. They can be identified by the hourglass pattern (red or orange in color) on the ventral aspect of their shiny, black abdomen (Figure 1). Male widow spiders are much smaller and lighter in color, and they lack the ability to deliver venom. Black widow spiders are commonly found in garages, trash heaps, and outbuildings but are uncommon in occupied dwellings. Bites are usually defensive, occurring when the spider is accidentally disturbed.4 Black widow spider envenomation remains a significant health problem in the US, being reported over 2500 times annually to US poison-control centers.1,2 The actual number of envenomations is probably much higher, because poison-center estimates tend to underreport exposures.6 Black widow spider envenomation frequently results in severe pain, muscle cramps, abdominal pain, back pain, and hypertension. These symptoms may be refractory to traditional therapies. However, envenomation is associated with low mortality.4,7 Only three cases of deaths associated with widow spiders have been reported in the world medical literature. Two were patients from Madagascar bitten by L geometricus species, and the third was a young Greek woman who died of myocarditis after being bitten by an L tredecimguttatus spider.8,9 There are no known cases of death resulting from envenomation by the widow species found in the US. Antivenin Latrodectus mactans (Merck & Co, Inc, Whitehouse Station, NJ) is the only antivenom currently available in the US for treatment of black widow spider envenomation.10 Despite the significant symptoms that may develop after envenomation, the use of antivenom is a subject of debate within the toxicology community. This controversy stems primarily from a single reported case of fatal hypersensitivity related to spider antivenom administration. We describe here one case in which envenomation was treated without antivenom and three cases in which Antivenin Latrodectus mactans was used safely and effectively. Case Presentations Case 1 A previously healthy boy, age 3 years, arrived in the Emergency Department (ED) 1.5 hours after suffering a black widow spider bite to the top of his right foot while putting on his boots. The parents brought the spider to the ED, where it was identified as a female black widow. There was a 2-by-2-cm area of mild erythema to the top of the boy’s foot. Over the next hour, the boy developed severe foot, leg, groin, and abdominal pain. His vital signs were as follows: blood pressure, 111/68 mmHg; respiratory rate, 20 to 30 breaths/min; heart rate, 103 beats/min; temperature, 98.4°F; pulse oxygen saturation, 99% on room air. His lungs were clear, and findings on his cardiac and abdominal examinations were normal. He cried constantly and complained of severe pain. The patient was treated with morphine and lorazepam in the ED, which did not provide relief. Because of concern about a hypersensitivity reaction, he was not given Antivenin Latrodectus mactans. He was eventually admitted to the pediatric ward for further pain control. In the hospital, he received ketorolac every 6 hours and hydromorphone every 4 hours for 2 days. A consultation with the Medical Toxicology Service was not obtained. On the third hospital day, the boy began to feel better and was discharged to his home that afternoon. After discharge, his symptoms resolved completely, and he had experienced no further sequelae when evaluated 6 months later. Case 2 A previously healthy man, age 35 years, arrived in the ED approximately 1 hour after sustaining a bite to his left middle toe from what he described as a “black spider.” He was doing yard work, wearing boots that were “open at the top,” when he felt a sudden pain in his toe. When he removed the boot to investigate, a black spider ran out. Within 5 minutes of the incident, he began feeling severe pain, cramping, and paresthesias in his left leg. The pain progressed to include his abdomen, low back, and chest. In the ED, the patient complained that the pain was so severe that it was difficult to sit or lie down. Because the patient’s description of the spider that bit him and the classic clinical syndrome, his symptoms were believed to be caused by Latrodectus envenomation. His vital signs were as follows: blood pressure, 146/72 mmHg; respiratory rate, 18 breaths/min; heart rate, 71 beats/min; temperature, 97.8°F; pulse oxygen saturation, 99% on room air. He appeared uncomfortable and was treated with intravenous diazepam and ketorolac, which did not provide relief. During his ED stay, his pain became more severe, requiring multiple doses of hydromorphone for control. The patient stood bent over the gurney and appearing very uncomfortable. His lungs were clear, and findings on his cardiac and abdominal examinations were normal. His left middle toe showed no discernible bite marks, swelling, or erythema. Because of the patient’s severe pain, the medical toxicologist thought that Latrodectus antivenom would be appropriate for treatment. The benefits and risks of treatment were discussed, and then the patient stated, “I would rather die taking the medicine than feel the pain the way I do.” One vial of Antivenin Latrodectus mactans (2.5 mL) was infused intravenously during a 30-minute period. Within 15 minutes of infusion completion, he began experiencing relief. No further hydromorphone was required. He was observed in the ED for 2 hours and then discharged to his home. A follow-up appointment was scheduled for 48 hours later, but he did not keep it. A review of the medical records showed no return visits to the ED and no further clinic visits by the patient. He was not available for long-term follow-up assessment. Case 3 A woman, age 24 years, arrived in the ED and said that she had sustained a black widow spider bite on her right shoulder. The spider was on a shirt that she put on. The patient had mild erythema without swelling at the bite site. She complained of severe pain and muscle cramps in the shoulder, neck, and back. Her vital signs were as follows: blood pressure, 143/94 mmHg; respiratory rate, 18 breaths/min; heart rate, 101 beats/min; temperature, 97.8°F; pulse oxygen saturation, 99% on room air. She appeared extremely uncomfortable. Her lungs were clear, and findings on her cardiac and abdominal examinations were normal. She was treated with hydromorphone, ketorolac, metoclopramide, and lorazepam, which provided minimal relief. Latrodectus antivenom therapy was recommended by the medical toxicologist because of her severe pain. After intravenous infusion of a single vial (2.5 mL) of Antivenin Latrodectus mactans, the patient experienced significant relief and required no further pain medication. She was discharged to her home after 2.5 hours of observation. She did not return to the ED or to her primary physician for further treatment. At a follow-up evaluation more than 1 year after the incident, she reported having no further sequelae after leaving the ED and no symptoms of serum sickness. Case 4 A boy, age 8 years, was brought to the ED by his mother approximately 3 hours after sustaining a black widow spider bite to his right second toe. The spider was in a shoe that the boy put on. The mother had brought the spider to the ED, and it was clearly identifiable as a female black widow. The patient complained of severe pain that began in his foot and then progressed to his leg, low back, abdomen, and chest. At presentation, his vital signs were as follows: blood pressure, 134/92 mmHg; respiratory rate, 26 breaths/min; heart rate, 96 beats/min; temperature, 97.8°F; pulse oxygen saturation, 96% on room air. He appeared to be in distress. He was diaphoretic. His abdomen was tight, and he exhibited diffuse guarding. His lungs were clear, and findings on his cardiac examination were normal. There was mild erythema of his right second toe, but there were no identifiable puncture marks. While in the ED, the patient began to complain of difficulty breathing. He was treated with morphine and diazepam, which did not provide relief. Latrodectus antivenom was recommended by the on-call toxicologist for treatment of his severe pain. A single vial (2.5 mL) of Antivenin Latrodectus mactans was infused intravenously during a 20-minute period. During infusion, he began experiencing relief of his symptoms. Within 20 minutes, he was feeling better and described his pain as being at a level of 1 on a scale of 1 to 10. After 1.5 hours of observation in the ED, he was released to his home. He was seen for a follow-up evaluation 2 days later and reported no further pain and had required no oral pain medication. At a follow-up evaluation more than 1 year later, he reported no further sequelae and no symptoms of serum sickness. Discussion Of the four cases discussed here, three involved bites to the feet and one to the right shoulder. One patient was treated without antivenom, and the other three patients were successfully and safely treated with Antivenin Latrodectus mactans. We believe that the rapid symptomatic improvement and favorable outcomes we observed in these cases were directly attributable to the use of spider antivenom. Antivenom provides rapid pain relief and may help to avoid hospital admissions and/or repeat ED visits. Latrodectus venom is one of the most potent poisons by volume, containing at least five insecticidal toxins, a vertebrate-specific neurotoxin (α-latrotoxin), and one toxin affecting crustaceans. The primary toxin responsible for the envenomation syndrome in humans is α-latrotoxin. The neurotoxin binds to specific presynaptic receptors (neurexin 1a and CIRL) that precipitate neurotransmitter release, particularly norepinephrine and acetylcholine.4 Release of these neurotransmitters is responsible for the classic envenomation syndrome seen with these bites. Black widow spider bites occur most commonly to the lower extremities, followed by the upper extremities and then the trunk.3,11,12 Interestingly, reports of early series noted higher numbers of bites to the trunk (ie, the buttocks and genitalia) related to outhouse exposures.13 No association between bite location and envenomation severity has been found.7 Local bite site findings are variable, including tiny puncture marks, mild erythema, and an erythematous target-like lesion11,14 (Figure 2). Symptoms of envenomation include diaphoresis, hypertension, muscle cramping, weakness, and pain either near or distant from the site of envenomation. The most common presenting symptoms are abdominal and/or back pain that may be very severe and difficult to treat (Table 1). Severe abdominal pain mimicking “acute abdomen” has even been reported.15 Although these symptoms can be extremely uncomfortable, permanent disability and death are rare.4,7 Treatment of black widow spider envenomation can be challenging, often necessitating large doses of pain medication and/or hospital admission. In one study, 52% (39 of 76) of patients with black widow bites who did not receive antivenom required hospital admission for further treatment.3 The traditional therapies for black widow spider envenomation are aimed at providing symptomatic relief while venom effects resolve. These include primarily opioid analgesics and muscle relaxants. Past trials involving these therapies have shown partial success at best.3,4,6,16 In addition, calcium therapy was once considered to be an antidote for black widow envenomation.17 Calcium was thought to stabilize nerve membrane permeability, resulting in decreased neurotransmitter release.16,17 Although this effect was demonstrated in vitro and reported in some early clinical series,13,16-18 subsequent experience has not shown effectiveness. Therefore, calcium therapy has lost favor in the medical toxicology community.3–6 The only therapies with proven effectiveness are opioid analgesics and black widow spider antivenom. Antivenin Latrodectus mactans is an equine-derived antivenom based on immunoglobulin G.4,10,19,20 The proposed pharmacologic mechanism is binding of venom toxic constituents by the antivenom antibodies. A single vial (2.5 mL) generally provides adequate relief in human (adult or pediatric) poisoning cases.3-5,14,19,21 The Kaiser Permanente (KP) acquisition cost for one vial of Antivenin Latrodectus mactans was $27.71 in 2011. In the largest series reported to date of moderate to severe black widow spider envenomation (n = 163), patients treated with antivenom experienced a much shorter duration of symptoms and were less likely to be admitted to the hospital than those who did not receive antivenom.3 Relief of symptoms occurred within an average of 31 minutes of antivenom infusion.3 Administration of antivenom even late in the course of envenomation has been reported to be effective.21,22 In one reported case, antivenom was used effectively for the treatment of symptoms 90 hours after a black widow spider bite.22 Acute hypersensitivity reactions are the most feared complication associated with Antivenin Latrodectus mactans administration. Although these reactions do occur, relatively few minor reactions have been reported,3,6,14 and only one report of a severe reaction can be found in the medical literature.3 Unfortunately, that one case is frequently cited as the reason to avoid administering antivenom to symptomatic patients.3,6 Critics believe that because black widow spider envenomation is generally a nonfatal condition, it is too risky to administer such treatment with even a single reported fatality reported in the medical literature. The case at the heart of controversy, however, involved a young woman with history of asthma and multiple medication allergies who received a rapid, undiluted bolus of antivenom. She had a severe hypersensitivity reaction. Unfortunately, her resuscitation was complicated by a pneumothorax and a protracted hospital stay, and she eventually died.2,3,6 Although that case was tragic, we do not believe that it represents sufficient evidence for abandoning antivenom use on the grounds that it is unsafe. The current package insert for Antivenin Latrodectus mactans calls for infusion of diluted antivenom during a period of 15 to 30 minutes.10 At these slower infusion rates, immediate hypersensitivity appears to be extremely rare.6 We believe that antivenom, when given correctly, is safe and should be considered in cases of envenomation with systemic symptoms or severe local symptoms. Though it is not mentioned on the package insert for Antivenin Latrodectus mactans, patients may be pretreated with diphenhydramine and/or steroids in an attempt to blunt a hypersensitivity response.5,6 Multiple allergies, asthma, or past reactions to equine-based products should be considered contraindications.10 Black widow spider envenomation in pregnancy has been recommended as an indication for antivenom because of the risk of venom-induced abortions or other possible harm to the fetus4,23; however, the actual risk is not known. In one report of a poison-center study of 97 black widow spider bites in pregnant females, there were no miscarriages.24 Although Antivenin Latrodectus mactans is a category C drug, it has been given in pregnancy without consequence.25,26 Even though absolute safety is impossible to prove, there is nothing currently to suggest that spider antivenom is unsafe in pregnancy. Antivenin Latrodectus mactans does contain the preservative thimerosal, but the amount of mercury associated with an antivenom dose would not be expected to cause fetal harm.24 The package insert for Antivenin Latrodectus mactans does warn of the potential for (delayed) serum sickness after antivenom administration. In contrast to equine-based snake antivenom (Antivenin Crotalidae Polyvalent [Wyeth-Ayerst, West Greenwich, RI]), which required much larger doses and was associated with serum sickness in the majority of patients, Latrodectus antivenom usually requires only a single vial, and there are few reports of serum sickness from it.5,6,14 Although the exact rate of serum sickness after black widow spider antivenom is unknown, our review of the literature leads us to believe that it is low. In one study of Australian red-back spider antivenom (a similar antivenom product, Antivenin Latrodectus hasselti [CSL Limited, Parkville, Victoria, Australia]), the incidence of serum sickness was 1.7%.11 Antivenin Latrodectus mactans has been used for more than 70 years. A new Fab antibody-based antivenom is currently in development and in phase 3 trials. The hope is that this product will be equally effective but carry a lower risk of hypersensitivity reactions. KP Northern California has a regional on-call Medical Toxicology consultation service offering assistance in treating poisoned patients. Conclusion In three of four cases of symptomatic black widow spider envenomation, we administered Antivenin Latrodectus mactans and observed rapid and complete resolution of symptoms. These cases demonstrate the safe and effective use of spider antivenom. Our review of the literature suggests that the witnessed effects of antivenom are usual, which leads us to believe that Antivenin Latrodectus mactans is safe when given correctly. Disclosure Statement This study received no funding. The author(s) have no conflicts of interest to disclose. Acknowledgment Katharine O’Moore-Klopf, ELS, of KOK Edit provided editorial assistance. References 1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 26th annual report. Clin Toxicol (Phila) 2009 Dec;47(10):911–1084. 2. Daly FFS, White J. Widow and related Latrodectus spiders. In: Brent J, Wallace K, Burkhart K, Phillips S, Donovan J, eds. Critical care toxicology: diagnosis and management of the critically poisoned patient. Philadelphia, PA: Elsevier Mosby; 2005. p 1187–93. 3. Clark RF, Wethern-Kestner S, Vance MV, Gerkin R. Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med 1992 Jul;21(7):782–7. 4. Hahn IH, Lewin NA. Arthropods. In: Flomenbaum NE, Goldfrank L, Hoffman R, Howland MA, Lewin N, Nelson L. Goldfrank’s toxicologic emergencies. 8th ed. New York: McGraw-Hill Professional; 2006. p 1603–22. 5. Peterson ME. Black widow spider envenomation. Clin Tech Small Anim Pract 2006 Nov;21(4):187–90. 6. Clark RF. The safety and efficacy of antivenin Latrodectus mactans. J Toxicol Clin Toxicol 2001;39(2):125–7. 7. Moss HS, Binder LS. A retrospective review of black widow spider envenomation. Ann Emerg Med 1987 Feb;16(2):188–92. 8. Ramialiharisoa A, de Haro L, Jouglard J, Goyffon M. [Latrodectism in Madagascar]. [Article in French]. Med Trop (Mars) 1994;54(2):127–30. 9. Pneumatikos IA, Galiatsou E, Goe D, Kitsakos A, Nakos G, Vougiouklakis TG. Acute fatal toxic myocarditis after black widow spider envenomation. Ann Emerg Med 2003 Jan;41(1):158. 10. Antivenin Latrodectus mactans [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2005. 11. Sutherland SK, Trinca JC. Survey of 2144 cases of red-back spider bites: Australia and New Zealand, 1963–1976. Med J Aust 1978 Dec 30;2(14):620–3. 12. Isbister GK, Gray MR. Latrodectism: a prospective cohort study of bites by formally identified redback spiders. Med J Aust 2003 Jul 21;179(2):88–91. 13. Kirby-Smith HT. Black widow spider bite. Ann Surg 1942 Feb;115(2):249–57. 14. Nordt SP, Lee A, Sasaki K, Clark RF, Cantrell FL. Retrospective review of black widow spider antivenom use [abstract 110]. Clin Toxicol 2010;48(6):627. Available from: www.eapcct.org/publicfile.php?folder=congress&file=Abstracts_Denver.pdf. 15. Bush SP. Black widow spider envenomation mimicking cholecystitis. Am J Emerg Med 1999 May;17(3):315. 16. Key GF. A comparison of calcium gluconate and methocarbamol (Robaxin) in the treatment of Latrodectism (black widow spider envenomation). Am J Trop Med Hyg 1981 Jan;30(1):273–7. 17. Gilbert EW, Stewart CM. Effective treatment of arachnidism by calcium salts: a preliminary report. Am J Med Sci 1935;189(4):532–6. 18. Timms PK, Gibbons RB. Latrodectism—effects of the black widow spider bite. West J Med 1986 Mar;144(3):315–7. 19. Bronstein NA. Antidotes in depth: antivenom (scorpion and spider). In: Flomenbaum NE, Goldfrank L, Hoffman R, Howland MA, Lewin N, Nelson L. Goldfrank’s toxicologic emergencies. 8th ed. New York: McGraw-Hill Professional; 2006. p 1623–8. 20. Heard K, O’Malley GF, Dart RC. Antivenom therapy in the Americas. Drugs 1999 Jul;58(1):5–15. 21. Suntorntham S, Roberts JR, Nilsen GJ. Dramatic clinical response to the delayed administration of black widow spider antivenin. Ann Emerg Med 1994 Dec;24(6):1198–9. 22. O’Malley GF, Dart RC, Kuffner EF. Successful treatment of latrodectism with antivenin after 90 hours. N Engl J Med 1999 Feb 25;340(8):657. 23. Russell FE, Marcus P, Streng JA. Black widow spider envenomation during pregnancy. Report of a case. Toxicon 1979;17(2):188–9. 25. Wolfe MD, Meyers O, Carvati EM, Rayburn WF, Seifert SA. Black widow spider envenomation in pregnancy. J Matern Fetal Neonatal Med 2011 Jan;24(1):122–6. 26. Sherman RP, Groll JM, Gonzalez DI, Aerts MA. Black widow spider (Latrodectus mactans) envenomation in a term pregnancy. Curr Surg 2000 Jul 1;57(4):346–8. 27. Handel CC, Izquierdo LA, Curet LB. Black widow spider (Latrodectus mactans) bite during pregnancy. West J Med 1994 Mar;160(3):261–2. 28. Quan D, Ruha AM. Priapism associated with Latrodectus mactans envenomation. Am J Emerg Med 2009 Jul;27(6):759.e1–2. 29. Sari I, Zengin S, Davutoglu V, Yildirim C, Gunay N. Myocarditis after black widow spider envenomation. Am J Emerg Med 2008 Jun;26(5):630.e1–3. 30. Hoover NG, Fortenberry JD. Use of antivenin to treat priapism after a black widow spider bite. Pediatrics 2004 Jul;114(1):e128–9.
Gastric Antral Vascular Ectasia (Watermelon Stomach)--An Enigmatic and Often-Overlooked Cause of Gastrointestinal Bleeding in the Elderly
Friday, 02 July 2010
Hien Nguyen, MD; Connie Le, MD; Hanh Nguyen, MD Fall 2009 - Volume 13 Number 4 Abstract Gastric antral vascular ectasia (GAVE) syndrome, also known as watermelon stomach is a significant cause of acute or chronic gastrointestinal blood loss in the elderly. is characterized endoscopically by “watermelon stripes.” Without cirrhosis, patients are 71% female, average age 73, presenting with occult blood loss leading to transfusion-dependent chronic iron-deficiency anemia, severe acute upper gastrointestinal bleeding, and nondescript abdominal pain. Introduction Gastric antral vascular ectasia (GAVE) syndrome, also known as watermelon stomach, is a rare but significant cause of severe acute or chronic gastrointestinal blood loss in the elderly.1–4 Although it is associated with heterogeneous medical conditions, including hepatic, renal, and cardiac diseases, its pathogenesis is unknown.1-3 The diagnosis of GAVE syndrome in patients with renal or hepatic disease is often problematic because there are more frequent causes of gastrointestinal bleeding in these diseases (vascular malformations, peptic ulcer disease, esophageal or gastric varices, and colonic and rectal ulcers) that overshadow GAVE syndrome. Furthermore, diagnosis may be challenging because gastrointestinal bleeding may be occult or overt, and the endoscopic appearance of GAVE syndrome resembles that in portal hypertensive gastropathy (PHG) or antral gastritis. However, differentiation of GAVE syndrome from these other causes is critical because of the vastly disparate therapies required for each. Building on a leading theory that mechanical stress is involved in the pathogenesis, we speculate that the diverse medical risk factors may be related to GAVE syndrome through an autonomic dysfunction.5,6 Case Report A woman, age 63 years, with a chronic hepatitis C infection, esophageal varices, and hemodialysis-dependent end-stage renal disease secondary to diabetes and hypertension presented at our institution and reported several weeks of intermittent generalized abdominal pain and vomiting and daily minimal stools that appeared blood-streaked on wiping but without hematemesis or melena. Laboratory findings showed a hemoglobin of 6.8 g/dL; a hematocrit of 20%; and normal hepatic function, platelet count, prothrombin time, and international normalized ratio. Although the anemia was consistent with iron deficiency, the low hemoglobin level invariably decreased to pretransfusion levels within days of blood transfusion. Contrast computed tomography scan of the abdomen revealed hepatomegaly but no other significant gastrointestinal pathology. Because our patient had had endoscopically proven portal esophageal varices and PHG two years before we examined her, which had been treated with sclerotherapy and propranolol, esophagogastroduodendoscopy was repeated in anticipation of further sclerotherapy for esophageal varices, PHG, or peptic ulcer disease. Instead, a repeat endoscopy revealed extensive vascular ectasias and patchy erythema in the distal antrum that were diagnostic of GAVE syndrome, but no esophageal or gastric varices. A colonoscopy showed hemorrhoids. It was thought that hemorrhoidal bleeding alone could not explain the severe and relapsing anemia, and GAVE syndrome was considered a more plausible cause of severe anemia from gastrointestinal blood loss. The endoscopist considered primary medical therapy with laser photocoagulation but because of the presence of diffuse and advanced vascular ectasias did not believe that this would be sufficient and would not produce long-lasting results. The patient was notified of the higher risks of definitive surgery in light of her multiple comorbidities and underwent an uncomplicated subtotal gastrectomy without a long-term need for blood transfusions. Discussion Although GAVE syndrome is a rare medical condition, it is a relevant possibility in older patients with severe acute or chronic gastrointestinal blood loss, because it accounts for up to 4% of nonvariceal upper gastrointestinal blood loss.1–4,7 The initial presentation may include occult blood loss leading to transfusion-dependent chronic iron-deficiency anemia, severe acute upper-gastrointestinal bleeding, nondescript abdominal pain, or even gastric outlet obstruction, as described in a prior case report. This disease entity was first described by Rider et al1 in a patient with severe chronic iron-deficiency anemia and gastroscopy showing “fiery red changes with marked hypertrophic mucosal changes, and scattered profuse bleeding.” A majority of patients without cirrhosis but with GAVE syndrome are female (71%) with median age of 73 years, whereas the majority of patients with both cirrhosis and GAVE syndrome are male (75%) with a mean age of 65 years.1,2 Associated medical conditions include heart, liver, and kidney diseases; diabetes; connective-tissue diseases; hypothyroidism; and status as a bone marrow transplant recipient.1–4 The epidemiologic features of GAVE syndrome are attributed to the age and sex distributions of the underlying medical conditions, of which connective-tissue diseases and cirrhosis are the most commonly related.1,2 The syndrome has the name watermelon stomach because of the pathognomonic endoscopic appearance (columns of red tortuous ectatic vessels along longitudinal folds of the antrum) that resembles watermelon stripes (Figure 1 and 2).1–5 Typical histologic changes include superficial hyperplastic antral mucosa, capillary ectasia with thrombosis, and fibromuscular hypertrophy of the lamina propria.1–4 GAVE syndrome is often misdiagnosed on endoscopy as PHG. Unlike watermelon stomach, PHG causes predominant changes in the fundus and corpus.1,2 GAVE syndrome does not respond to measures that decrease portal pressures in PHG, including transjugular intrahepatic shunt and β-blocker therapy.1,2,4,7 Therapy for GAVE syndrome can be separated into three categories: pharmacologic, endoluminal, and surgical approaches.1,2,7–9 Pharmacologic therapies have been described with the use of corticosteroids, estrogen–progesterone combinations, tranexamic acid (with a significant risk of ischemic events and pulmonary emboli), thalidomide, α-interferon, calcitonin, and cyproheptadine.1,2 However, the effectiveness of all these medications have been described only in reports of single cases or small case series.1,2,7,8 Endoluminal therapies are the mainstay of conservative management and include endoscopic band ligation, sclerotherapy, heater probe, and argon plasma coagulation, which is emerging as the preferred endoscopic therapy.1,2 Although multiple intraluminal treatment sessions may be required for cessation of transfusion dependence, the safety of endoscopic therapy is well documented, and there is only a single case report of a complication --gastric outlet obstruction secondary to argon plasma coagulation.8 Further, a recent case report described successful endoscopic mucosal resection of lesions in GAVE syndrome with resolution of anemia.9 There is a paucity of reports of controlled studies of GAVE syndrome in terms of medical versus surgical therapy. The consensus, however, is that primary surgical therapy is not advocated, because of reports of high morbidity and mortality from patients undergoing surgery with GAVE syndrome who often have multiple other serious medical comorbidities. However, Novitsky et al4 have argued for a somewhat more aggressive surgical approach as second-line therapy, especially in patients in whom a short trial of endoluminal treatment fails. They argue that antrectomy is the only reliable therapy with definitive and curative potential, especially for unresponsive or severe disease. Minimally invasive laparoscopic antrectomy has also been advocated as a novel approach to the therapy of GAVE syndrome.10 Furthermore, treatment of underlying medical conditions can lead to resolution of GAVE syndrome.1,2,4,7 For instance, liver transplantation has been reported to lead to complete resolution of GAVE syndrome.1,2 Our case presentation demonstrates the therapeutic dilemmas in this problematic disease, whereas reports of controlled studies comparing efficacy are lacking. Our patient possessed multiple medical comorbidities that placed her at higher surgical risk. Thus, she was initially referred to an endoscopist for the purpose of conservative intraluminal therapy with argon plasma coagulation. However, the endoscopist concluded that the patient’s particular mucosal lesions were so advanced and so diffuse that even intensive intraluminal therapy would be inadequate and would surely result in the need for multiple therapies that would produce questionable long-term control. This was significant because the patient had a history of lack of compliance, including regarding taking medications and keeping appointments for multiple medical evaluations across different specialties. The patient was advised about the risks and benefits of intraluminal versus surgical therapy, the latter of which the surgeon believed offered a more conclusive and definitive cure; the outcome was favorable. The pathogenesis of GAVE syndrome, principally considered an idiopathic disease, is unknown, and theories about it are controversial.1,2 An understanding of the pathophysiologic changes that lead to GAVE syndrome is lacking because most theories are based on single case reports or on reports of smaller series of fewer than 15 cases. However, a leading and plausible theory suggests antropyloric motility dysfunction.6 Quintero et al5 first conceptualized a theory of mechanical stress, where disordered peristaltic waves may cause partial prolapse of distal gastric mucosa through the pylorus, leading to formation of ectatic vessels.6 This disordered peristalsis and loss of gastric propulsive activity and motility may occur secondary to denervation of the digestive autonomic nervous system, which is primarily parasympathetic.6 The characteristic histologic finding of fibromuscular hyperplasia in GAVE syndrome further supports this hypothesis.1–6 We speculate that the altered gastric and antral motility in some patients with GAVE syndrome may be modulated by vagal denervation and sympathetic overactivity, which are already known to exist in many of the associated medical problems.5,6 Chronic liver disease is known to impair cardiovascular autonomic reflexes, whereas sympathetic overactivity is implicated in the pathogenesis and progression of renal diseases and heart failure.11–13 For several decades, it has been known that plasma norepinephrine levels are elevated in chronic renal failure, indicative of increased sympathetic nerve activity.12 Interestingly, recent research has hypothesized a role for the sympathetic nervous system in the modulation and expression of autoimmune lymphoproliferative and connective-tissue diseases such as systemic lupus erythematosus.14 Thus, these diverse medical conditions may share a common autonomic dysfunction with GAVE syndrome.12–14 In a retrospective chart review of our patient, we discovered that she had multiple symptoms suggestive of autonomic neuropathy and dysfunction, including neuropathy of the lower extremities, orthostatic hypotension, frequent hypoglycemia, and gastroparesis. Conclusion GAVE syndrome is an important diagnosis to consider in older patients with severe anemia and occult or profuse gastrointestinal bleeding, especially in the setting of heart, liver, or kidney diseases.1–4 The main inherent teaching point is that GAVE syndrome can be inadvertently overlooked as a remediable cause of gastrointestinal bleeding because there are more frequent causes of gastrointestinal bleeding (esophageal or gastric varices, PHG, and peptic ulcer disease) among patients with renal or hepatic diseases, which are the same medical conditions in which GAVE syndrome occurs. The endoscopic appearance of GAVE syndrome often mimics that of PHG or antral gastritis. Further, the case we reported here demonstrates that GAVE syndrome may be underdiagnosed because observational studies of screening gastroscopies in patients undergoing liver transplantation show that 1 in 40 patients has GAVE syndrome.1,2 Because this is a single-case report, we speculate that in larger case series, further studies of neurohormonal factors that may be involved in sympathetic nervous system dysfunction and disordered peristalsis in GAVE syndrome may provide more insight into the pathogenesis of this enigmatic disease.11–14 Disclosure Statement The author(s) have no conflicts of interest to disclose. Acknowledgments The authors would like to thank the Scleroderma Program, Division of Rheumatology, University of Michigan Medical Center for Figure 1 and the Pathology Department, University of Pittsburgh Medical Center for Figure 2. Katharine O’Moore-Klopf, ELS, of KOK Edit provided editorial assistance. References 1. Rider JA, Klotz AP, Kirshner JB. Gastritis with veno-capillary ectasia as a source of massive gastric hemorrhage. Gastroenterology 1953 May;24(1):118-23. 2. Selinger CP, Ang YS. Gastric antral vascular ectasia (GAVE): an update on clinical presentation, pathophysiology and treatment. Digestion 2008;77(2):131–7. 3. Stefandis I, Liakopoulos V, Kapsoritakis AN, et al. Gastric antral vascular ectasia (watermelon stomach) in patients with ESRD. Am J Kidney Dis 2006 Jun;47(6):e77–82. 4. Novitsky YW, Kercher KW, Czerniach DR, Litwin DE. Watermelon stomach: pathophysiology, diagnosis, and management. J Gastrointest Surg 2003 Jul–Aug;7(5):652–61. 5. Quintero E, Pique JM, Bombi JA, et al. Gastric mucosal vascular ectasias causing bleeding in cirrhosis. A distinct entity associated with hypergastrinemia and low serum levels of pepsinogen I. Gastroenterology 1987 Nov;93(5):1054–61. 6. Charneau J, Petit R, Calès P, Dauver A, Boyer J. Antral motility in patients with cirrhosis with or without gastric antral vascular ectasias. Gut 1995 Oct;37(4):488–92. 7. Dulai GS, Jensen DM, Kovacs TO, Gralnek IM, Jutabha R. Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension. Endoscopy 2004 Jan;36(1):68–72. 8. Farooq FT, Wong RC, Yang P, Post AB. Gastric outlet obstruction as a complication of argon plasma coagulation for watermelon stomach. Gastrointest Endosc 2007 Jun;65(7):1090–2. 9. Kastsinelos P, Chatzimavroudis G, Katsinelos T, et al. Endoscopic mucosal resection for recurrent gastric antral vascular ectasia. Vasa 2008 Aug;37(3):289–92. 10. Sherman V, Klassen DR, Feldman LS, Jabbari M, Marcus V, Fried GM. Laparoscopic antrectomy: a novel approach to treating watermelon stomach. J Am Coll Surg 2003 Nov;197(5):864–7. 11. Stadlbauer V, Wright GA, Banaji M, et al. Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology 2008 Jan;134(1):111–19. Erratum in: Gastroenterology 2008 Mar;134(3):897. Stadlbauer V, Mookerjee RP. 12. Vonend O, Rump LC, Ritz E. Sympathetic overactivity--the Cinderella of cardiovascular risk factors in dialysis patients. Semin Dial 2008 Jul–Aug;21(4):326–30. 13. Goldsmith SR. Interactions between the sympathetic nervous system and the RAAS in heart failure. Curr Heart Fail Rep 2004 Jul;1(2):45–50. 14. del Rey A, Besedovsky HO. Sympathetic nervous system-immune interactions in autoimmune lymphoproliferative diseases. Neuroimmunomodulation 2008;15(1):29–36.
Humanizing Patients through Narrative Approaches: The Case of Murphy, the “Motor-Mouth”
Tuesday, 08 June 2010
Michael Pickren Valenti, MA; Lewis Mehl-Madrona, MD, PhD, MPhil Summer 2010 - Volume 14 Number 2 Abstract Background: Some psychiatric patients are presented as hopeless, burned out, and devoid of social graces. Staff of mental health centers and hospitals are not encouraged to view these people differently. A narrative perspective allows anyone to emerge as a richly complex human being. Method: A course presented students with the opportunity to create narrative descriptions of patients presented by medical staff as hopeless. Results: One student’s narrative of “Murphy the Motor Mouth” is presented; it shows the validity and usefulness of the narrative approach in reconstructing a person to be avoided as an interesting, valuable, and richly complex human being. Conclusion: Murphy in story emerges as more interesting and worthy of knowing than the clinical Murphy constructed by medical staff. Narrative approaches offer a richness and intimacy that fosters a more therapeutic and effective relationship between patients and staff. Introduction In our contemporary psychiatric settings, patients are sometimes presented as hopeless, recalcitrant, and “burned out.” In this article we present the result of the interaction of a faculty and a student to change a “burned-out” patient into an interesting person through elicitation of his narrative. Narrative medicine has emerged as a new approach to humanize medicine,1 along with promoting empathy,2 and inculcating cultural competence.3 These approaches have not necessarily failed, but medicine still contains powerful dehumanizing influences.4 Methods As part of a course in narrative medicine, students were encouraged to find patients who had been dehumanized and to interview these patients to produce a narrative of interest about people who had been previously presented as uninteresting and burned out. The patient described herein was presented as a hopelessly recalcitrant “bipolar” with no redeeming social graces. We present an alternative narrative to show how narrative approaches can redeem the hopelessly lost, at least in the eyes of their caregivers, and foster more effective treatment. Results The story: Murphy, the “Motor-Mouth” was a special patient, but the staff at the hospital didn’t agree. His big presence, loud voice, and insatiable thirst for interaction were dramatic. He often laughed and made the sterile halls of the hospital come to life. But no one was laughing with him. I (MPV) was informed that Murphy was a Bipolar I substance abuser whose energy needed constant pharmaceutical correction. The staff hesitantly concurred that he was an interesting person, but tenaciously resisted the urge to know him. Yet, to me Murphy continued to stand out. The superficial level with which he had been conveyed became clear as I got to know him. Murphy presented as a tall, well-built male in his early ﬁfties. His raspy voice projected from a large mouth with few teeth. He frequently asked, “How are you doing?” and cheerfully waved from across the room. Murphy loved to tell old stories, new stories, or retold stories. Once he got going, one could sit back and enjoy a fairly linear, often fast and disorganized, cascading monologue. Murphy was a Caucasian and Paciﬁc Islander mixed male born in Provo, UT. He was raised in a large Mormon family with three brothers and ﬁve sisters. Murphy enjoyed a stable childhood with a family rooted in faith. He never experienced abuse or neglect. Murphy recalled ﬁshing as a child and legendary moments in high school football. He boastfully shared many nicknames including “Kuntukinte,” “Dizzy D,” and “Baby Brain,” but could not recall their origin or meaning. After high school Murphy joined the military. He favorably recalled his time in Korea. Murphy loved the food and the people. He said “I felt love with the people” and “I ate kim chee.” His time in Korea also increased his appreciation for the US. He said, “People here are spoiled brats; they don’t know. They’re just used to having food every day.” He did not experience trauma in the service and was discharged after two years. A few years after his military service, Murphy experienced two traumatic events: witnessing the murders of his girlfriend and cousin. These events took place in his early thirties. Murphy appeared impenetrable to sadness until these memories emerged. They could silence a Murphy monologue above all else. Despite his high energy, Murphy’s ideology was easygoing. He was a person of the people, someone who did not strive for riches and power. Murphy often felt misunderstood and found refuge from judgment with his friends. Murphy claimed to “hang out with handicap people because they accept [him] for who [he is]” and said “[His] friends work at McDonalds.” Murphy experimented with drugs and alcohol at an early age. He was smoking cigarettes in the third grade and by the eighth grade using alcohol, marijuana, LSD, and cocaine. He used LSD every day in the summertime as a late adolescent. Despite his avid use, Murphy felt he was cautious. He “[found] out what [was] safe.” He did not blindly use any drug that came his way; Murphy did his homework. He read books and sought information before feeling comfortable with a substance. Murphy claimed drugs didn’t affect his mind and that they were “just an experience.” He was impenetrable to the effects of drugs. Murphy felt drugs played little part in his life path or current predicament. Despite his research and cautiousness, Murphy did experiment with some extremely dangerous substances. He used ice and sniffed paint, yet remained unscathed. Murphy was a proud marijuana smoker. He animatedly illustrated the joy of using marijuana in all its varieties. He felt it brought friends together and enhanced life. Murphy’s legal and psychiatric history were unclear. Murphy served ﬁve years in prison for robbing a bank. He said he was wrongly convicted, but wanted to serve the time and move on with his life. Murphy was diagnosed with Bipolar I disorder in his early thirties after “staying up for six days and six nights.” His ﬁrst manic episode appeared to have followed the deaths of his cousin and girlfriend. However, because of Murphy’s often tangential, disorganized, and fast speech, he could not construct a coherent timeline. Murphy did not feel he had a mental illness; rather, a “motor mouth because doctors only give him a limited time to talk.” Doctors had not listened to him in the past and “[he knew] what it is like not to be heard.” Murphy loved to “talk story.” He was mostly interested in talking about life. When asked to talk about his experiences with pharmacologic agents, he often sidetracked. At the time of the class, he was taking lithium (600 mg twice daily), aripiprazole (30 mg daily), and benzotropine mesylate. He was ﬁrst placed on lithium subsequent to his Bipolar I diagnosis. He felt very similar on or off drugs. When asked why he took medication, Murphy said, “Because I claim disability and my doctors think I am safe.” However, the medications gave him substantial digestive side effects. He recalled diarrhea so severe that “[he] kept wiping [himself], ….” Murphy told many stories of being unable to get to the bathroom fast enough and enduring this very tangible consequence. However, all the side effects disappeared when he took benzotropine mesylate. Murphy spoke highly of benztropine mesylate and treated it as a saving grace. He insisted on taking benzotropine mesylate while on any psychoactive medication. Without it, the side effects were unbearable. Benzotropine mesylate was Murphy’s favorite drug. He said it reduced his digestive symptoms. Benzotropine mesylate is known to cause euphoria and excitement. Murphy could have been enjoying the side effects rather than the drug’s primary mechanism. Passion can be expressed in many ways. Some endure years of practice and devote countless hours to perfect a craft. This brand of passion is most familiar to our modern day society. Yet, how many forms can passion take? Must it be hardworking? Murphy was a man of passion. He devoted himself to a lifestyle. From a young age he passionately sought an easy “feel-good sensation.” He walked a path of least resistance to a place of highest pleasure. Undoubtedly, this passion led to drug use. Drugs meet all Murphy’s criteria. To Murphy, his behavior was not a bad habit or pathology, it was him. In accordance with his philosophy, he didn’t resist physician’s orders. Rather, he took the prescribed drugs, added one for entertainment, and continued to live out his passion. Sparring with an opponent who rolls with every punch inevitably leads to the aggressor being unwilling to enter into the dance of the defendant. Murphy took the lead and all medicine could do was to avoid stepping on his toes. Conclusion “In a larger sense, the biological study of mind is more than a scientific inquiry of great promise; it is also an important humanistic endeavor. The biology of mind bridges the sciences—concerned with the natural world—and the humanities—concerned with the meaning of human experience. Insights that come from this new synthesis will not only improve our understanding of psychiatric and neurological disorders, but will also lead to a deeper understanding of ourselves.” —Eric Kandel, MD5 Narratives give physicians the skills, methods, and texts to learn how to imbue the facts and objects of health and illness with their consequences and meanings for individual patients and physicians.1,6,7 The narrative about Murphy was more humanizing than the clinical story circulating among the medical staff. In the above story, Murphy emerged as a competent, optimizing, goal-directed human being in stark distinction to the role cast by the medical staff as burned out, hopeless, uninteresting, and annoying. The shift of focus from clinical to narrative allows us to consider the impact of this change of focus. The patient comes to the clinician with a story to tell and wants someone else to hear this story and to reverence it.8 But the clinician's role is not simply to be the passive hearer, but to become a participant-observer and a listener. Our narratives carry important messages, both to ourselves and to whomever we are asking to listen. Murphy’s narrative carries a message of competence in contradistinction to the usual clinical narrative of incompetence in which he is usually presented. He maintains an aura of joy in a usual story of despair. A narrative perspective allows Murphy to be seen in all his complexity: his strengths, his joys, his weaknesses, and his despair. All of these operate for such a richly complex individual. A narrative perspective enriches ordinary clinical care and humanizes medicine to appreciate people as more than their diagnosis and symptoms. It exposes students to narrative ideas while studying standard clinical presentations and it allows students to appreciate the richness of human life over the reductionism of much of clinical science. For this reason, it should be encouraged within the clinical sciences. At the University of Hawaii, we are beginning to create a Narrative Medicine program to humanize the clinical sciences and to create bridges with the indigenous medicines of the Pacific Rim, which are decidedly based upon stories and the healing impact of “talking story.” Murphy is one of the many patients who would benefit from a narrative approach to psychiatry. Rita Charon, MD writes that “Narrative medicine has evolved as a means to honor the stories of illness, whether told by the patient, family member, doctor, or nurse. More sharply it has become a way to probe the narrativity of disease, of health, of healing, and of the relation between the sick person and the one who tries to help.”1 One’s story is more than “just” information. It is us giving to another a part of our soul: our essence. A person’s story is more than a case history of symptoms to be noted as part of a medical assessment; it is something to be prized and honored. Writing of time spent with her patients, Charon has this to say “Through the attention I donate and the authenticity he displays, we grow together in knowledge, in action and in grace, hoping for the best, making it out together …”1 This makes narrative into a shared experience where both clinician and patient can give to each other and learn from each other. Over the past five decades research has demonstrated the immense importance of therapeutic alliance, empathy, and collaboration. Successful treatment is reliably predicted by the presence of these three factors. The aforementioned variables were nonexistent between Murphy and the staff. Murphy was presented to Michael, the student from a distant and critical perspective in which the patient was receiving treatment. The staff offered little interest in Murphy’s perspective as his job was to take what he was given. This is not Murphy’s first stay at the hospital and it likely won’t be his last. Patients like Murphy are often regarded as “treatment failures.” Yet, in the absence of the three most crucial elements of effective treatment, it appears that he’s not failing treatment; treatment is failing him. Viewing patients through a narrative lens turns a clinical case into a person. When patients become people, collaboration and empathy exist more naturally and the patient enters into a bilateral relationship. The narrative approach is not simply a way to conceptualize, rather a catalyst for the implementation of more effective treatment of our mentally ill. Disclosure Statement The author(s) have no conflicts of interest to disclose. References 1. Charon R. The patient-physician relationship. Narrative medicine: A model for empathy, reflection, profession, and trust. JAMA 2001 Oct 17;286(15):1897-902. 2. DasGupta S, Charon R. Personal illness narratives: using reflective writing to teach empathy. Acad Med 2004 Apr;79(4):351-6. 3. DasGupta S, Meyer D, Calero-BreckheimerA, Costley AW, Gullen S. Teaching cultural competency through narrative medicine: intersections of classroom and community. Teach Learn Med 2006 Winter;18(1):14-7. 4. Coulehan J. Metaphor and medicine: narrative in clinical practice. Yale J Bio Med 2003;76(2):87-95. 5. Kandel ER. Biology and the future of psychoanalysis: a new intellectual framework for psychiatry revisited. Am J Psychiatry 1999 Apr;156(4):505-24. 6. Brody H. Stories of sickness. New Haven: Yale University Press; 1987. 7. Kleinman A. The illness narratives: suffering, healing and the human condition. New York: Basic Books; 1998. 8. Rudnytsky PL, Charon R. Psychoanalysis and narrative medicine (S U N Y series in psychoanalysis and culture). Albany, NY: State University of New York Press; 2008.
Peripartum Cardiomyopathy: Case Reports
Friday, 02 July 2010
Mary Wang, MD Fall 2009 - Volume 13 Number 4 Abstract Peripartum cardiomyopathy (PPCM) is a dilated cardiomyopathy defined as systolic cardiac heart failure in the last month of pregnancy or within five months of delivery. PPCM, which affects thousands of women each year in the US, was first described in the 1800s, yet its etiology is still unclear. Its diagnosis is often delayed because its symptoms closely resemble those within the normal spectrum of pregnancy and the postpartum period. When PPCM is misdiagnosed or its diagnosis is delayed, the consequences for patients are deadly: The disorder carries a high mortality rate. Introduction Peripartum cardiomyopathy (PPCM) is associated with one in every 3000 to 4000 live births, affecting thousands of women in the US each year.1 The definition of PPCM includes four criteria: 1) development of cardiac failure in the last month of pregnancy or within five months of delivery, 2) absence of an identifiable cause for the cardiac failure, 3) absence of recognizable heart disease before the last month of pregnancy, and 4) left ventricular (LV) dysfunction (ejection fraction of less than 45% or reduced shortening fraction).2,3 Risk factors include multiparity, black race, older maternal age, pre-eclampsia, and gestational hypertension.1,4 Symptoms of PPCM, which include fatigue, edema, and dyspnea, are similar to those for the normal spectrum of peripartum states and pregnancy comordities such as pulmonary emboli and eclampsia.5 Therefore, diagnosis is often delayed and the disorder is under recognized, with devastating consequences: Mortality is as high as 20% to 50%.5 The following two case reports illustrate a typical presentation and an atypical one. This article also reviews the etiology, clinical symptoms, treatment, and prognosis for PPCM, which must be understood to provide patients with the most efficient and appropriate care. Case 1 A white woman, age 29 years, presented to our urgent-care clinic five days after giving birth, reporting dyspnea and fatigue that had lasted two days. She said that because this was her first pregnancy, she thought her symptoms to be normal after delivery. However, when her husband insisted, she went to the clinic for evaluation. She was found to be dyspneic and hypoxic with saturation on room air in the low 80th percentile and was sent to the Emergency Department (ED) for further treatment. Her medical history included obesity, but the patient was in relatively good health until approximately her last month of pregnancy, when she developed gestational hypertension (without other significant pre-eclampsia signs and symptoms), dependent peripheral edema, as well as some symptoms of an upper respiratory infection. She was given labetalol, 200 mg orally, twice daily, for blood-pressure management. During examination in the ED, the patient was noted to be afebrile and had a blood pressure of 156/88 mm Hg, a pulse rate of 90 beats per minute, a respiratory rate of 20 breaths per minute, and an oxygen saturation of 95% while receiving oxygen through a 2-L nasal cannula. Her lungs were clear to auscultation and her heart rate was regular, with an S3 gallop. Her extremities were nonedematous, and she had no calf tenderness. Urinalysis results were negative for any proteins. Plasma levels of D-dimer and circulating levels of B-type natriuretic peptide (BNP) were 1981 pg/mL and 864 pg/mL, respectively. An electrocardiogram showed a normal sinus rhythm. Chest radiographs showed cardiomegaly with increased vascular congestion bilaterally. A computed tomography (CT) chest scan to evaluate for possible pulmonary emboli showed evidence of pleural effusion and cardiomegaly but no emboli. The patient was subsequently admitted to the hospital for new-onset PPCM and was given furosemide intravenously for diuresis. A transthoracic echocardiogram done at admission showed an LV ejection fraction of 35% to 40%, with trace aortic and mitral regurgitation. Her fatigue and dyspnea greatly decreased with diuresis; she was discharged from the hospital three days later and instructed to take lisinopril and labetalol. Follow-up examination at six months showed a stable cardiomyopathy and well-controlled hypertension, and a repeat echocardiogram at the same point showed an improved ejection fraction of 55% to 60%. Case 2 A white woman, age 25 years, presented at the ED with dyspnea six days after having given birth for the first time. She reported not having had any coughing, chest pain, or calf pain. Her medical history was significant for hypothyroidism, for which she was taking levothyroxine. Her pregnancy had been otherwise noneventful, except for flulike symptoms approximately one month before childbirth that included coughing, nausea, vomiting, and diarrhea. In the ED, the patient appeared to be slightly anxious. She had a blood pressure of 159/87 mm Hg, a pulse rate of 58 beats per minute, a respiratory rate of 20 breaths per minute, and an oxygen saturation of 100% on room air. Physical examination showed no jugular venous distention, S3 heart sound, edema, or hepatosplenomegaly. She was slightly tachypneic but not in any acute respiratory stress. Laboratory tests revealed no proteinuria and a BNP level of 272 pg/mL. Echocardiography showed a normal sinus rhythm at 46 beats per minute. Chest radiograph findings were noted to be normal, with no cardiomegaly or pulmonary congestion. A CT scan of the chest was negative for pulmonary emboli. The patient was discharged from the care of the ED physician with a diagnosis of dyspnea secondary to breast enlargement versus chest wall pain. She kept an appointment in our family medicine clinic four days later for a follow-up examination and still had the same symptoms. An echocardiogram ordered at that time showed left atrial and LV dilation, global LV hypokinesis, and an estimated ejection fraction of 25% to 30%. A cardiology consultation was done and the patient was given appropriate medications for heart failure, which alleviated her symptoms. Her follow-up echocardiogram three months later showed normalization of her ejection fraction to 60%. Discussion Approximately 60% to 70% of women experience a sensation of dyspnea during the course of normal pregnancy.6 Although historically PPCM risk factors occur in older women and in black women, contemporary trends show that there is an increasing incidence (24%–37%) in young primigravid and white patients.7–9 The details of the two cases reported here support this trend; the women are both young primigravidas and are white. Because dyspnea is a common finding in normal pregnancy and even in the initial postpartum state, PPCM is often missed, especially if the patient population does not fit the typical epidemiology. Etiology A possible relationship between pregnancy with dilated cardiomyopathy was recognized as early as the 1870s10 and was classified as a distinct clinical entity in the 1930s.11 Yet the cause of PPCM is still unknown. Most postulate that it is related to the cardiovascular stress of pregnancy (increased fluid load); others have suggested myocarditis. Felker et al12 found that 26 of 51 women with PPCM had histologic evidence of myocarditis on endomyocardial biopsy. Other researchers further postulate that PPCM may be an inflammatory response in pregnancy, citing an elevation of tumor necrosis factor-alpha and interleukin-6 levels.13,14 Some evidence also suggests that it may be a pathologic autoimmune response to fetal cells that lodge in the maternal circulation and cardiac tissue.3 There is also conflicting evidence whether nutritional deficiencies--more specifically, selenium deficiency--is a cause for PPCM.15,16 Clinical Features and Diagnosis Clinical features of PPCM include symptoms of congestive heart failure and chest pain. Signs can include tachycardia, tachypnea, pulmonary rales, an enlarged heart, and an S3 heart sound.4 Such signs and symptoms overlap with those of many other conditions, ranging from normal pregnancy to pulmonary emboli and upper respiratory infection (Table 1). Diagnosis of PPCM includes the four criteria described at the start of this report. There are no specific laboratory abnormalities for PPCM, although BNP is often elevated. However, other exclusionary laboratory studies should also be considered, including cardiac enzymes assessment and a pre-eclampsia workup. Imaging studies include electrocardiography, chest radiography, and echocardiography. Electrocardiographic findings are often normal but can include sinus tachycardia, nonspecific ST- and T-wave abnormalities, and voltage abnormalities.17 Chest radiographs can show signs of pulmonary congestion, cardiac enlargement, and even pleural effusions in some cases.9 Echocardiograms usually show decreased contractility and LV enlargement without hypertrophy.18 Treatment and Prognosis The treatment for PPCM is the same as for other forms of congestive heart failure (fluid and salt restriction, β-blocker, diuretic, and digoxin), except for angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, which are contraindicated in pregnancy.1 Hydralazine can be used during pregnancy to reduce afterload.4 Diuretics can be used cautiously during pregnancy to prevent dehydration and placental insufficiency. Patients with PPCM are also at high risk for thrombus formation;19 thus, anticoagulation should be considered especially for high-risk patients with severe LV dysfunction. In addition, physical activity should be encouraged according to patients’ tolerance of symptoms. The best time to discontinue these medications is unknown, but their use should be continued for at least one year.7 If medical treatments are not successful, heart transplantation is often the last resort. Fortunately, in recent years, the rate required transplantation has decreased to about 4% to 7%.20 Transplantation success rates are good with favorable long-term survival rates.21 In about 50% of patients, the ejection fraction normalizes. Regardless of recovery, however, a second pregnancy is usually not recommended for these patients because PPCM recurs in more than 30% of subsequent pregnancies, which puts both mother and baby at great risk.1 Conclusion The cases presented here demonstrate the variability of clinical presentation of PPCM. Case 1 illustrates a typical PPCM presentation, with gestational hypertension, S3 gallop, hypoxia, an elevated BNP level, cardiomegaly, and pulmonary congestion on chest radiographs. Case 2 illustrates an atypical PPCM presentation, with no abnormal findings on physical or imaging studies, yet with a lower ejection fraction shown by echocardiography. Thus, it is important that physicians be familiar with PPCM and therefore consider it when diagnosing dyspneic patients to expedite medical treatment for a potentially lethal condition. Disclosure Statement The author(s) have no conflicts of interest to disclose. Acknowledgment Katharine O’Moore-Klopf, ELS, of KOK Edit provided editorial assistance. References 1. Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald’s heart disease: a textbook of cardiovascular medicine. 8th ed. Philadelphia, PA: Saunders; 2007. p. xx–yy. 2. Demakis JG, Rahimtoola SH, Sutton GC, et al. Natural course of peripartum cardiomyopathy. Circulation 1971 Dec;44(6):1053–61. 3. Pearson GO, Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA 2000 Mar 1;283(9):1183–8. 4. Marx JA, Hockberger RS, Walls RM, eds. Rosen’s emergency medicine: concepts and clinical practice. 6th ed. Philadelphia, PA: Elsevier Health Sciences; 2006. 5. Abboud J, Murad Y, Chen-Scarabelli C, Saravolatz L, Scarabelli TM. Peripartum cardiomyopathy: a comprehensive review. Int J Cardiol 2007 Jun 12;118(3):295–303. 6. Simon PM, Schwartzstein RM, Weiss JW, Fencl V, Teghtsoonian M, Weinberger SE. Distinguishable types of dyspnea in patients with shortness of breath. Am Rev Respir Dis 1990 Nov;142(5):1009–14. 7. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet 2006 Aug 19;368(9536):687–93. 8. Amos AM, Jaber WA, Russell S. Improved outcomes in peripartum cardiomyopathy with contemporary. Am Heart J 2006 Sep;152(3):509–13. 9. Bhakta P, Biswas B, Banerjee B. Peripartum cardiomyopathy: review of the literature. Yonsei Med J 2007 Oct 31;48(5):731–47. 10. Cunningham GF, Gant NF, Leveno KJ, Gilstrap III LC, Hauth JC, Wenstrom KD, eds. Williams Obstetrics. 21st ed. New York: McGraw-Hill; 2001. p 1141–514. 11. Hull E, Hafkesbring E. “Toxic” postpartal heart disease. New Orleans Med Surg J 1937;89:550-7. 12. Felker G, Thompson R, Hare J, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000 Apr 13;342(15):1077–84. 13. Sliwa K, Skudicky D, Bergemann A, Candy G, Puren A, Sareli P. Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1. J Am Coll Cardiol 2000 Mar 1;35(3):701–5. 14. Sliwa K, Förster O, Libhaber E, et al. Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. Eur Heart J 2006 Feb;27(4):411–6. 15. Cénac A, Simonoff M, Moretto P, Djibo A. A low plasma selenium is a risk factor for peripartum cardiomyopathy. A comparative study in Sahelian Africa. Int J Cardiol 1992 Jul;36(1):57–9. 16. Fett JD, Ansari AA, Sundstrom JB, Combs GF. Peripartum cardiomyopathy: a selenium disconnection and an autoimmune connection. Int J Cardiol 2002 Dec;86(2–3):311–6. 17. Davidson NM, Parry EH. The etiology of peripartum cardiac failure. Am Heart J 1979 Apr;97(4):535–6. 18. Lampert MB, Lang RM. Peripartum cardiomyopathy. Am Heart J 1995 Oct;130(4):860–70. 19. Walsh JJ, Burch GE, Black WC, Ferrans VJ, Hibbs RG. Idiopathic myocardiopathy of the puerperium (postpartal heart disease). Circulation 1965 Jul;32:19–31. 20. Felker G, Jaeger CJ, Klodas E, et al. Myocarditis and long-term survival in peripartum cardiomyopathy. Am Heart J 2000 Nov;140(5):785–91. 21. Rickenbacher PR, Rizeq MN, Hunt SA, Billingham ME, Fowler MB. Long-term outcome after heart transplantation of peripartum cardiomyopathy. Am Heart J 1994 May;127(5):1318–23.
A Case of an Abdominal Mass: Follicular Lymphoma
Wednesday, 21 December 2011
Tina L Walker, MD, Gabriel E Lopez, MD Fall 2011 - Volume 15 Number 4 Abstract Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma. The disease usually affects older individuals, with the average age at diagnosis being 63.5 years. Only in 4% of cases is the disease diagnosed in individuals younger than age 40 years. The case presented in this report describes the diagnosis of FL in a 38-year-old woman and highlights the variability of this disease. Tumor grading, disease staging, and the Follicular Lymphoma International Prognostic Index score can be valuable aids in prognosis. Treatment consists of close observation or radiation therapy for early-stage disease, and rituximab with combination chemotherapy regimens for more advanced disease. Cure is rare. Treatment is predominately handled by oncologists, but these patients will likely first present to their primary care physicians. Symptoms can be subtle at times, so it is essential to be able to recognize them to provide the patient with timely treatment. Introduction Lymphomas are divided into two general categories, Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). NHL is far more common than Hodgkin lymphoma.1 Differences between these two major types of lymphoma can be detected by microscopy. Within these two large groups, there are a myriad of subtypes. Of instances of NHL, 22% are follicular lymphoma (FL). Diffuse large B-cell lymphoma is the most common lymphoma in the US, and FL is the second most common.1 The mean age of persons in Sweden when their FL is diagnosed is 63.5 years, and only 4% are younger than age 40 years at time of diagnosis.2 Presentation varies widely among patients with FL. It can include palpable adenopathy detected by the patient or clinician during examination. Adenopathy can be present peripherally throughout the body, including in the cervical, axillary, and inguinal areas. Often adenopathy is intermittent, with waxing and waning symptoms, for unclear reasons. It can also take the form of palpable abdominal masses, which can be asymptomatic or can cause obstructive symptoms in the gastrointestinal or genitourinary tract.3 Systemic complaints, or B symptoms, are reported in approximately 20% of patients with FL4 and consist of fever, unexplained weight loss, and profuse night sweats. Considering the vagueness of symptoms or the lack of symptoms altogether, the variation in patients’ presentation is considerable. This can make detecting FL in the primary care setting a challenge. Because the presenting symptoms of fatigue and lymphadenopathy are so nonspecific, the diagnosis of FL is frequently delayed, and disease is usually found in multiple sites once discovered. The following case illustrates a presentation of FL in the primary care setting and the diagnostic testing that revealed its presence. Case Report A 38-year-old Hispanic woman presented to our clinic with pain in the center of her lower abdomen. The pain was sharp, constant, and severe and radiated to her back. Symptoms had begun three days earlier and were getting worse. She reported feeling feverish and chills intermittently during the preceding three days. She also described, on questioning, increased urinary frequency during that time. Her medical history included a previous diagnosis of Hashimoto thyroiditis and bilateral conductive hearing loss. She had three pregnancies and has two children. She had a diastasis recti separation in the abdominal wall noted after the birth of her last child. She was taking no medications regularly. She reported never smoking, never taking street drugs, and drinking alcohol sparingly. Her family history provided no additional information. On examination, the patient was in no distress. Her temperature was 37.3°C (99.1°F); blood pressure, 101/69 mm Hg; pulse, 105 beats per minute, and respirations, 20 breaths per minute. Her height was 1.626 m (5'4"), and her weight was 59.603 kg (131 lb 6.4 oz). Her weight was essentially unchanged during the preceding year. There was no palpable adenopathy. Her heart rhythm was regular, and her lungs were clear. A large diastasis recti separation was felt in the center of the abdomen, which was also noted on examination two months before this visit. A large, firm, tender, mobile mass was palpated in the left lower quadrant of her abdomen. The abdominal mass was initially thought to be an enlarged spleen, and an ultrasound was ordered. The patient’s condition was diagnosed as cystitis, and she was given trimethoprim-sulfamethoxazole, 160-800 mg, as oral tablets, which she took twice daily for 10 days. Laboratory tests were ordered. Urinalysis showed a specific gravity of 1.004. All other components of urinalysis were within normal limits. A urine culture yielded no growth. The patient’s hemoglobin level was 12.3 g/dL, and her white blood cell count was 10,600 per mm3 (10.6 × 109 per liter), with 82.2% neutrophils. Serum electrolyte, blood urea nitrogen, and creatinine levels were within normal limits. Her alanine aminotransferase and aspartate aminotransferase levels were within normal limits, as was the total bilirubin level. Findings on the mononucleosis test for heterophile antibody were negative. An abdominal ultrasound revealed a 8.4 × 6.8 × 7.5 cm heterogeneous solid mass in the anterior lower left. Of note, an ultrasound of the abdomen produced unremarkable findings 7 months earlier when the patient presented with right-sided flank pain. A computed tomography (CT) scan of the abdomen and pelvis was suggested and performed with administration of oral and intravenous contrast. CT scans showed a large, lobulated mass within the left small-bowel mesentery (Figure 1). Mesenteric vessels in the area were encased. There were several adjacent prominent lymph nodes within the mesentery of the small bowel. The state of other abdominal and pelvic organs were unremarkable, as was that of bony structures. There was no bowel obstruction. The Surgery Department recommended a CT-guided needle biopsy of the mass. This was performed, and the pathology findings were FL, grade 3. Immunohistochemistry showed a B-cell type with positive findings for cluster of differentiation (CD) 10, CD20, B-cell lymphoma 2 (BCL-2), and BCL-6. The patient was referred to the Oncology Department. Her serum lactate dehydrogenase level was within normal limits at 132 IU/L. Positron-emission tomography (PET) scanning revealed lymphoma, and no disease was seen above the diaphragm, in the spleen, or in the bone marrow (Figure 2). Bone marrow biopsy showed no evidence of involvement by lymphoma. A multigated acquisition scan was performed, and the patient’s cardiac ejection fraction was measured at 67%. She underwent six cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). A subsequent PET scan obtained 2.5 months after the first scan showed complete response of the lymphoma to therapy, with no evidence of active residual lymphoma (Figure 3). The Oncology Department continues to monitor her closely. Discussion Although the genetic hallmarks involved in FL have been extensively studied, the pathogenesis is not completely understood. In up to 90% of cases, there are breakpoint regions in chromosome 18 and reshuffled aspects of BCL-2.5,6 A resulting translocation, t(14;18), leads to an increased expression of BCL-2, an oncogene that hastens apoptosis and leads to increased cell survival time.7 FL develops from follicle B cells, including both centrocytes (smaller) and centroblasts (larger) types of cells.8 Obtaining a tissue sample for histologic analysis is paramount in the diagnosis and grading of FL. Excision of an enlarged lymph node or core needle biopsy of a mass aids in the identification of FL. Fine-needle aspiration can miss the diagnosis of lymphoma and, if performed, should always be followed by a tissue biopsy.9 Establishing FL grade requires attention to the proportion of centroblasts present. Aggressive FL has more centroblasts, and the higher number of these cells, the higher the grade of the FL, with grade 3 being the highest assignable grade.10 Blood tests and bone marrow analysis are also routinely done, in addition to immunohistochemistry of the biopsy sample. There is also the Follicular Lymphoma International Prognostic Index (FLIPI), which can be helpful when considering prognosis in FL. The FLIPI score can be calculated by assigning one point to each of these criteria: age >60 years, serum lactate dehydrogenase level above normal, a hemoglobin level of <12.0 g/dL, designation of stage 3 or intravenous FL, and the number of involved nodal areas >4.11 A higher FLIPI score places the individual at higher risk of dying. A score of 0 to 1 is considered low risk, 2 is intermediate, and 3 to 5 is high risk. The patient described here had a FLIPI score of 2 (one point for the stage and the other for the number of lymph nodes involved). Staging of FL examines the number of involved lymph nodes and describes the anatomic extent of the disease. The overall course of FL varies widely. Some patients have swift tumor growth and spread, leading to enlargement of lymph nodes and organs, causing discomfort and possibly obstruction. Others opt not to receive treatment and may live free of symptoms for years. Spontaneous regression of FL has also been observed.12 FLIPI score and tumor grade are useful indicators for prognosis of FL and can aid in determining the course that the disease will take. Treatment of FL is contingent on the stage of the disease. Radiation to the involved area is the treatment of choice in the early stages.13 Stage 1 FL involves one lymph node region and potentially an extralymphatic site (stage 1E). Stage 2 has two or more lymphatic regions involved on the same side of the diaphragm and may also involve an extralymphatic site (stage 2E).14 Radiation therapy is the treatment of choice for FL in stages 2 and 3, with 10-year survival reported to be between 60% and 80%.15 Chemotherapy is indicated in more advanced stages of FL. Stage 3 involves lymphatic regions on both sides of the diaphragm. Stage 3 can include involvement of the spleen (stage 3S), adjacent extralymphatic sites (stage 3E), or both (stage 3ES). Stage 4 disease involves one or more extralymphatic site(s) diffusely.14 Treatment regimens of the more advanced stages of FL often include the monoclonal antibody agent rituximab. The use of this agent, along with combination chemotherapy, has shown to provide better control of the disease and increased survival.16 Several chemotherapeutic agents are combined for the treatment of FL. The R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) combination can be used, as can this same set of medications with added doxorubicin (R-CHOP). There is no single standard of care when selecting the combinations of medications, and the treated patients comprise a heterogeneous group in which outcomes fluctuate and are complex to quantify.17 Patients should be monitored at regular intervals for relapse. A favorable response to treatment is initially widespread across cases of FL, but there is no cure for the disease. Relapse is common, as is the likely progression of FL.18 It is important for patients with FL to be provided with information regarding their disease. Understanding lymphoma as an entity can be daunting for patients. Testing, diagnosis, staging, grading, prognosis, and disease progression can be overwhelming and complicated. Therefore, it is imperative that both the oncologist and those in primary care monitor for relapse and assist the patient in understanding the disease. Conclusion Although much of the diagnosis and treatment of FL will be carried out by oncologists, initially patients with FL will likely find themselves in the office of their primary care physician. The road that unfolds before the patient can include fear-provoking imaging, biopsies, tumor grade and immunohistochemistry assignments, staging, and treatments. Familiarity with the presentation, etiology, and treatment of FL will help clinicians better serve their patients. The average age of patients at diagnosis of FL is 63.5 years. The case described here involves a 38-year-old woman. This disparity highlights one aspect of the variable presentation of FL. Inconsistencies also exist from individual to individual in respect to the progression and course of FL. Treatment options and combinations for FL are many. None are curative. Patients diagnosed with FL require monitoring at regular intervals and support from both their specialists and their primary care physicians. More information for patients, their families, and their clinicians can be found at www.cancer.org, www.cancer.gov, and www.lls.org. Disclosure Statement The author(s) have no conflicts of interest to disclose. Acknowledgment Katharine O’Moore-Klopf, ELS, of KOK Edit provided editorial assistance. References 1. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol 1998 Aug;16(8):2780–95. 2. Goldin LR, Björkholm M, Kristinsson SY, Turesson I, Landgren O. Highly increased familial risks for specific lymphoma subtypes. Br J Haematol 2009 Jun;146(1):91–4. 3. Krikorian JG, Portlock CS, Cooney P, Rosenberg SA. Spontaneous regression of non-Hodgkin’s lymphoma: a report of nine cases. 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Long-term outcome and mortality trends in early-stage, Grade 1–2 follicular lymphoma treated with radiation therapy. Int J Radiat Oncol Biol Phys 2006 Mar 1;64(3):928–34. 16. Salles G, Mounier N, de Guibert S, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008 Dec 15;112(13):4824–31. 17. Friedberg JW, Taylor MD, Cerhan JR, et al. Follicular Lymphoma in the United States: first report of the national LymphoCare Study. J Clin Oncol 2009 Mar 10;27(8):1202–8. 18. Cheson BD, Pfistner B, Juweid ME, et al; International Harmonization Project on Lymphoma. Revised criteria for malignant lymphoma. J Clin Oncol 2007 Feb 10;25(5):579–86.