A 23 yo AA girl with PMH of asthma was admitted to the hospital with a 3 day history of generalized muscle pain.

LEARNING OBJECTIVES:  1. Recognize unusual etiologies of localized lymphadenopathy. 2. Recognize clinical features of Castleman’s disease. 3. Determine when there is a need for biopsy in patients presenting with lymphadenopathy.

CASE:  A 53 year old Caucasian male presents with left groin lump and 10 kg weight loss over a period of one month. The lump is painful to touch and has been progressively enlarging in size over the past month. The patient also complains of generalized malaise and night sweats. His past medical history is significant for essential hypertension. The physical exam reveals an ill-appearing, 72 inch, 81 kg male with stable vital signs. The general physical exam is unremarkable except for a left sided groin mass measuring 2 –3 cm in size. The mass is discrete, firm and mobile with moderate tenderness to touch and not associated with erythema or induration. Laboratory exam initially reveals a normal CBC and differential and normal electrolytes. An ultrasound of the groin mass reveals clusters of enlarged inguinal lymph nodes, the largest of which measures 3.6 cm. A CT scan of the chest, abdomen, and pelvis reveals no additional lymphadenopathy. An inguinal lymph node biopsy was done, with initial pathology impression being a low grade lymphoma, but a second opinion from a reference laboratory was reported as follicular hyperplasia with expanded mantle zones, atretic germinal centers and monotypic lambda expression by plasma cells (Castleman’s disease like changes).

DISCUSSION:  Lymphadenopathy is often a diagnostic challenge for general internists. There is a rather large list of possible etiologies, some of which require immediate attention and management. Definitive diagnosis is often obtained by biopsy, which is invasive and not necessary in some cases. The role of general internists is crucial to identifying patients who require lymph node biopsy through a detailed history and physical exam. Age, location, duration, and associated signs and symptoms aid in deciding when a biopsy is necessary. The presence of enlarging lymphadenopathy and systemic symptoms in this patient indicate the need for a lymph node biopsy. Castleman’s disease or angiofollicular lymph node hyperplasia is an uncommon etiology of lymphadenopathy that was first described by Benjamin Castleman. Castleman’s disease can present as localized lymphadenopathy (unicentric Castleman’s disease) or generalized lymphadenopathy (multicentric Castleman’s disease). These two forms of disease carry different prognoses. Unicentric Castleman’s disease, as was found in this case, is potentially curable with surgical excision of lymph node. Multicentric Castleman’s disease, in contrast, has a median survival of only 8 to 14 months. Clinically, it is difficult to differentiate Castleman’s disease from other more malignant lymphoproliferative disorders. Most cases of unicentric Castleman’s disease are asymptomatic, the median age of the patient is approximately 35, it occurs equally in males and females, and the median size of the lesion is 5 to 9 cm. Unicentric Castleman’s disease is of two subtypes: hyaline-vascular (90%) and the plasma cell type. The hyaline-vascular type is considered a reactive chronic lymphoid hyperplasia. The plasma cell type is considered to have an inflammatory pathogenesis, either through chronic antigenic stimulation (i.e. infection) or via an autoimmune mechanism. A plasma cell dyscrasia which includes polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS syndrome) is sometimes associated with Castleman’s disease. Interleukin-6 has been defined to have a role in the pathophysiology of this disease, and the systemic manifestations of Castleman’s disease. In contrast, multicentric Castleman’s disease usually occurs in patients with a median age between 52 and 65, and presents with systemic symptoms such as fever, malaise, weight loss, and peripheral lymphadenopathy. Hepatomegaly and splenomegaly are also common findings at presentation. Mediastinal and abdominal lymphadenopathy is less common at presentation although approximately 50% will progress to involve mediastinal or abdominal lymph nodes.

LEARNING OBJECTIVES:  To recognize the potential for topical anesthetic agents to cause severe allergic reactions, including anaphylaxis, in susceptible individuals.

CASE:  On the day of admission, a 73-year old man underwent a surveillance cystoscopy for transitional cell carcinoma of the bladder and dilation of a recurrent urethral stricture. During an uneventful 30-minute outpatient procedure, the patient received no medications other than 20 cc of a 2% lidocaine gel that was used as a topical anesthetic. Within 30 minutes of leaving the cystocopy suite, the patient developed intense pruritis and a feeling that he was about to pass out. The patient’s wife noticed that he was markedly weak and pale and she immediately brought him to the Emergency Room. Initial physical exam revealed a diaphoretic man with a blood pressure (BP) of 61/34 and a weak pulse at 76 beats/minute. The chest and heart exams were normal but a diffuse urticarial skin rash was noted on the trunk and extremities. The patient’s BP responded to the administration of two liters of IV normal saline and 50 mg of IV diphenhydramine. Additional medical history revealed that the patient had a previous allergic reaction to Bactrim that caused a similar urticarial skin rash. His active prescription list included propylthiouracil, lisinopril, felodipine and simvastatin for treatment of hyperthyroidism, hypertension and hyperlipidemia. None of these medications were new and the patient specifically denied use of any over-the-counter medications, supplements or nutraceuticals. A literature search determined that the formulation of topical lidocaine used in this case contained sodium metabisulfite, a sulfite responsible for causing allergic type reactions, including anaphylaxis, in susceptible individuals. The patient’s chart was subsequently marked ALLERGIC TO TOPICAL LIDOCAINE and an adverse drug reaction form was filed with the hospital pharmacy. After a brief period of hospital observation, the patient was discharged home in stable condition and an outpatient allergy appointment was scheduled for further evaluation and sensitivity testing.

DISCUSSION:  Although usually considered a benign agent, some commercially available formulations of topical lidocaine contain additives that have the potential to cause serious allergic reactions in susceptible individuals. This vignette reinforces the importance of obtaining a thorough allergic history before beginning any new medication or using a new formulation of a previously administered medication. Systemic absorption of topically applied medications can cause serious, and potentially life-threatening, complications.

LEARNING OBJECTIVES:  Learning Objectives: 1. Recognize possible causes of anemia in a young woman. 2. Recognize the hematologic side effects of Lamotrigine.

CASE:  A 28 yo African American female with a history of seizures was admitted for worsening shortness of breath and weakness. Review of systems was otherwise negative. Her seizures were partial complex seizures controlled with Lamotrigine and Levetiracetam. She had been seizure free for over 2 years. Her family history was positive for thyroid disease and iron deficiency anemia. She does not use alcohol, tobacco or street drugs. The patient’s vital signs were normal except for a regular heart rate of 108, and her physical exam was otherwise completely normal. Laboratory evaluation revealed Hemoglobin of 4 mg/dL, Hematocrit 8.8%, MCV 93 fL, MCH 32 pg, MCHC 34 g/dL, Platelets 117.000/mcL, WBC 3.000/mcL with 45% neutrophils, 2% bands, 42% lymphocytes, 3% monocytes, 8% nucleated RBCs, reticulocyte count 5%. Serum iron was 150 µg/dL, transferrin saturation 60% and ferritin 600 ng/mL. LDH, haptoglobin and indirect bilirubin were normal as well as her TSH, B12, folate, LFTs and sickle cell prep. Viral antibody titers were negative. Bone marrow biopsy showed trilineage hematopoiesis, marked erythroid predominance and marked megaloblastic changes.

DISCUSSION:  In this patient with anemia and seizure disorder, the differential diagnosis of severe anemia includes: 1. Hypoproliferative bone marrow (e.g. medication induced, viral infections, leukemic infiltration) 2. Maturation disorders including thalassemia, sideroblastic anemia; B12 or folate deficiency. 3. Hemorrhage or hemolysis. We can narrow our differential diagnosis based on the initial negative evaluation. The patient’s bone marrow has a poor reticulocyte response to this degree of anemia suggesting inefficient erythropoiesis. Viral infections affecting the bone marrow, particularly Parvo B19, can cause an aplastic crisis. However, her parvovirus antibodies were negative. The bone marrow biopsy with evidence of megaloblastic picture in the setting of normal B12, folate can be attributed to medications, particularly to Lamotrigine. Erythroblastopenic crisis secondary to Lamotrigine has been described. Inhibition of dihydrofolate reductase is probably the mechanism of erythroblastopenia and it occurs more often in patients with underlying abnormal hematopoiesis, such as heterozygous [beta]-thalassemia. That brings the question of possible underlying abnormality of hematopoiesis in our patient and need for further work up such as hemoglobin electrophoresis. Treatment with folinic acid results in complete resolution of the erythroblastopenic crisis. Using this therapeutic approach, long-term treatment with Lamotrigine can be administered without any further complication. However, because of the severity of anemia in our patient Lamotrigine was discontinued and her hemoglobin recovered.

LEARNING OBJECTIVES:  1. A high index of suspicion for ADF based on history and physical examination should be maintained in the presence of equivocal or even negative diagnostic tests. 2. The finding of a primary aortoduodenal fistula in a patient with previous aortic aneurysm repair is extremely rare.

CASE:  An 84-year-old male with past medical history of hypertension, congestive heart failure, aortic valve replacement (on warfarin) and AAA repair, presented with one episode of bright red blood per rectum. On physical examination, he was afebrile and vitals were stable. Orthostatic hypotension was absent. Hemoglobin was 12 gm/dL, BUN was 55 mg/dL, serum creatinine was 1.8 mg/dL and INR was 2.99. An emergent EGD revealed no active bleeding. An abdominal CT scan with IV contrast revealed a saccular aneurysm arising from the infrarenal abdominal aorta with contrast entering the distal duodenum. This was highly suspicious for an aortoenteric fistula. Vascular surgery was immediately consulted. The patient suffered another episode of bright red blood per rectum with massive exsanguination and died despite aggressive resuscitation efforts. An autopsy evidenced a fistulous communication between the atherosclerotic aneurysm of orta and the third part of the duodenum, proximal to the suture line of the previous vascular graft. This was consistent with a primary aortoduodenal fistula, as defined below, and was quite unexpected.the a

DISCUSSION:  A primary aortoduodenal fistula (PADF) is defined as a communication between the native aorta and the duodenum. In contrast, secondary aortoduodenal fistulas (SADF) arise between the suture line of a vascular graft and the duodenum and are far more common than PADFs. The most frequent cause of PADF is atherosclerosis. The triad of pain, GI bleeding and an abdominal mass is seen in only 40% of patients. The initial bleeding, commonly known as a `herald bleed’, is often transient and self limiting owing to thrombus formation. EGD is useful to refute other causes of GI bleeding, but does not rule out ADF, which is often in the distal duodenum. Abdominal CT is specific but has low sensitivity for ADF. Treatment consists of emergent exploratory laparotomy with graft repair of the aorta and closure of the fistula tract. A high index of clinical suspicion, based on history and physical examination, is the key to correct diagnosis. Although the suspicion for SADF was high, the presence of a PADF in our patient makes this case unique