A young woman with episodic angioedema, papilledema, and eosinophilia

Abstract

A 21-year-old Chinese woman presented to the Emergency Department with a 6-week history of progressive headache, blurred vision, exertional dyspnea and limb claudication, mild epistaxis, and heavy menses. This was preceded by a 15-month history of episodic erythematous maculopapular rash and limb swelling. She had no fever, weight loss, or night sweats. Her past history was significant for glucose-6-phosphate dehydrogenase (G6PD) deficiency and she was on nortriptyline for headaches. She was not sexually active, had not traveled, and used no recreational substances. This syndrome of headache, visual disturbance, claudication, and mucosal bleeding suggests disruption of the microvasculature and platelet dysfunction such as seen in hyperviscosity syndrome. Increased serum viscosity may be due to hypergammaglobulinemia (monoclonal or polyclonal) or cryoglobulinemia and may lead to neurologic defects, mucosal bleeding, and thrombosis. Increased cellular viscosity is seen in conditions such as acute leukemia (leukostasis), myeloproliferative neoplasms, or sickle cell crisis and typically affects small vessels of the lungs and brain. The limb claudication, neurologic symptoms, and skin rash may also indicate a systemic vasculitis. Her transient limb swelling suggests angioedema. G6PD deficiency is typically an X-linked recessive disorder and therefore unusual in females but a hemolytic workup is appropriate if she is anemic. Physical examination revealed a pale thin young woman. Her temperature was 36.88C, blood pressure 115/65 mmHg (no pulsus paradoxus), heart rate 130 beats per minute, respiratory rate 20 breaths per minute, and oxygen saturation 98% on ambient air. Head and neck examination revealed multiple bilateral 1–2 cm soft, mobile cervical lymph nodes. Her jugular venous pressure (JVP) was at the angle of her jaw while at 908 and she had a loud pulmonic component of the second heart sound (P2), but no right ventricular heave. Her liver edge was palpable 6 cm below the costal margin, the span was 18 cm by percussion, and there was no splenomegaly. Fundoscopy revealed papilledema with tortuous ‘‘sausage’’ vessels, indistinct optic disk margins and absence of arterial pulsations. The rest of her neurologic exam was unremarkable. She had no rash, swelling, or joint effusions. Bloodwork done 1 week before revealed white-cells 13.9 3 10 per liter, eosinophils 3 10 9.1 3 10 per liter (normal 0.7), hemoglobin 75 g per liter, platelet count 205 3 10 per liter, total protein 137 g per liter (normal 62–82), albumin 31 g per liter, and gamma globulin 91 g per liter (normal 5.1–15) with a focally increased gamma-globulin peak. Immunofixation revealed predominantly IgG with corresponding lambda and kappa light chain bands of equal intensity. Creatinine was 82 lmol per liter, and urine was negative for blood and protein. An abdominal ultrasound 1 week before showed mild hepatomegaly of 17.9 cm with porta-hepatis lymphadenopathy measuring up to 2.7 cm, but no splenomegaly and no other intra-abdominal lymphadenopathy. The markedly elevated immunoglobulin G (IgG) levels and papilledema confirm the hypothesis of hyperviscosity syndrome. Equal kappa and lambda light chain intensity indicates a polyclonal gammopathy, although with such high levels, a monoclonal element cannot be excluded. Structural causes of raised intracranial pressure must be ruled out. Polyclonal hypergammaglobulinemia and eosinophilia may be associated with connective-tissue disease such as the Churg-Strauss syndrome, lymphoproliferative disorders such as angioimmunoblastic T-cell lymphoma (AILT), and idiopathic eosinophilia. Malignancy and parasitic infection with multiorgan involvement (such as strongyloides stercoralis) should be ruled out. Medication reactions, atopic disease, and adrenal insufficiency may be associated with reactive eosinophilia and/or hypergammaglobulinemia but are unlikely in this case. She has evidence of pulmonary hypertension with right ventricular failure (elevated JVP, loud P2, and hepatomegaly). This may be related to hyperviscosity. Hyperviscosity increases the risk of vascular thrombosis, so an electrocardiogram and cardiac enzymes should be done, as well as a computed tomography pulmonary angiogram to rule out