Arthritis and Rash

Posted by Sara Fazio • March 29th, 2013

In the latest Case Record of the Massachusetts General Hospital, a 30-year-old man with a history of IV drug use was admitted to this hospital because of fever, myalgias, polyarthritis, and rash. Results of liver-function tests were notable for mildly elevated hepatic aminotransferase levels and a normal bilirubin level.

Adulterants are compounds added to street drugs to increase profits for the seller. Levamisole, a veterinary antihelminthic agent, has become the most common adulterant of cocaine. The prevalence of levamisole in samples of cocaine sold on the street is estimated to be as high as 70%. Levamisole can lead to a dramatic vasculopathy and even vasculitis of small and medium-size blood vessels, conditions that are characterized by thrombosis, leukocytoclasis, and necrotizing lesions in blood vessels. This syndrome is accompanied by a confusing array of autoantibodies, including high titers of antineutrophil cytoplasmic antibodies (ANCA), antiphospholipid antibodies, and antibodies to double-stranded DNA. The cutaneous vasculopathy induced by levamisole has a predilection for fatty tissues, often leading to large ulcerative and necrotic lesions of the breasts, thighs, and flanks that mimic warfarin-induced necrosis.  Distinctive necrosis of the earlobe is common.

Clinical Pearls

 What musculoskeletal symptoms may accompany hepatitis C (HCV) infection?

HCV may cause arthralgias in patients with rheumatoid-factor positivity, generally caused by the high prevalence of mixed cryoglobulins among patients with HCV. Most patients with type II or type III cryoglobulinemia test positive for rheumatoid factor because the IgM component of the mixed cryoglobulin is directed against the Fc portion of IgG, which is the definition of rheumatoid-factor activity. HCV-associated cryoglobulinemic vasculitis is generally accompanied by purpura with a predilection for dependent areas, particularly the legs.

 What are the manifestations of serum sickness associated with acute hepatitis B (HBV) infection?

In a minority of patients, acute infection with HBV causes a syndrome resembling serum sickness. Polyarthritis and urticaria almost always occur as part of the prodromal stage of the syndrome, preceding the icteric phase by several days to several weeks. These symptoms are usually abrupt in onset. The polyarthritis is symmetric, with a predilection for small joints of the hands and knees, and may appear in an additive or migratory pattern associated with morning stiffness. A rash occurs at approximately the same time as the arthritis in half of all cases. The rash is most often urticarial, but erythematous macules and papules and petechiae are also reported. The syndrome usually persists for days or weeks, with a mean duration of approximately 20 days. Patients often have both fatigue and generalized weakness at some point in the course of the illness. The joint and skin manifestations typically resolve completely before or at the onset of the icteric phase of hepatitis. Approximately 40% of patients with the syndrome ultimately become jaundiced.

Morning Report Questions

Q: What is the cause of serum sickness associated with HBV? 

A: Serum sickness is a disorder caused by antigen-antibody or immune complexes formed in association with antigen excess. A spectrum of biologically active immune complexes contributes to the inflammation associated with serum sickness. In general, they are small, soluble antigen-antibody complexes that are not removed by the phagocytic macrophages that reside in the liver and spleen. The resultant circulating immune complexes contribute to the vascular and cellular phases of inflammation. The diverse antigens are composed of epitopes of HBsAg, HBc, and viral DNA. Antibodies to these antigens bind their specific antigens and form immune complexes. Complement proteins and phagocytic cells are also required for the development of serum sickness.

Q: What are the characteristic serologies associated with early HBV infection? 

A: The characteristic laboratory features of acute HBV infection include the detection of HBV DNA and HBsAg, the production of IgM antibody against hepatitis B core antigen (HBc), and less often, the presence of hepatitis B e antigen (HBeAg). The level of circulating HBV DNA is also typically elevated. Taken together, these features result in a molecular and serologic profile that is diagnostic of acute HBV infection.

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