Livedo reticularis and Raynaud's phenomenon associated with cryoglobulinaemia but not related to hepatitis C virus in an HIV-1-positive patient

ARTICLE

Case report

The patient was a 32-year-old, white, heterosexual woman who was found to be HIV-1-positive in December 1992. She denied any risk factors for HIV infection. During 1993, she developed oral and esophageal candidiasis, and perianal abcesses. The patient worked at a restaurant and in March 1994 she developed oedema, cyanosis and severe pruritus on both hands, at first only after exposure to cold water, but subsequently it became permanent. She also had patchy livedo reticularis on the buttocks, lower abdomen, legs (Fig. 1), forearms and hands. She reported malaise, but no fever, arthralgia or purpura.

She was in stage IV C1 (CDC'86), had a CD4 lymphocyte count of 4 cells/mm³, and was under treatment with didanosine. Laboratory evaluation revealed a mixed polyclonal (type III) cryoglobulinaemia determined by serum immunofixation (Cryocrit was higher than 10%). No complement abnormality was detected, as complement components C3 and C4 were within normal limits (69 mg/dl and 26 mg/dl respectively). There was no evidence of systemic arterial disease, lymphoma, active infection or drug toxicity. Syphillis, Lyme disease, hepatitis A, B and C serologies were negative, as well as the complete group of serologies systematically performed in the Internal Medicine Service of our Hospital. There was no clinical or laboratory evidence of hepatitis in her past medical history. A cutaneous biopsy from a buttock showed a PAS-positive, eosinophilic substance in the lumina of some vessels in the pars papilaris, with vascular plugging, but no vasculitis.

The patient continued treatment with didanosine, and there was no reason to begin zidovudine therapy. Cetirizine 10 mg plus hidroxicine 25 mg was added. Symptoms slowly improved and completely disappeared after 6 months, which corresponded to the absence of cryoglobulins. During 1995, the patient developed pulmonary and disseminated tuberculosis, rosacea, cytomegalovirus chorioretinitis, and wasting syndrome. She died at the end of 1995 of pneumocystic pneumonia.

Discussion

Mixed cryoglobulins are immune complexes that may be found in many different diseases, sometimes only temporarily. These include autoimmune, lymphoproliferative and liver diseases, different infections and sarcoidosis. Taillan et al. [1] reported the first case of symptomatic cryoglobulinaemia in an HIV-infected patient, that was related to HCV infection. Stricker et al. [2] described a case of mononeuritis multiplex associated with cryoglobulinaemia in an HIV-positive patient, but the patient's hepatitis C serology status was not noted. Le Lostec et al. [3] reported a peripheral neuropathy associated with cryoglobulinaemia but not related to HCV infection in an HIV-infected patient. Gaffuri et al. [4] found a "positive cryoglobulin test" in an AIDS patient that turned out to be a case of cold agglutinin-associated hemolytic anemia without cryoglobulins.

Cutaneous symptoms are common in cryoglobulinaemia, but no cases had been described in HIV-infected patients until now. This is the only case of symptomatic cryoglobulinaemia found in our prospective study of 1,161 HIV- infected patients [5]. Our patient showed livedo reticularis and Raynaud's phenomenon, that are well known cutaneous symptoms of cryoglobulinaemia in HIV-negative patients. She did not develop purpura, but it is well known that cryoglobulinaemia can occur without vasculitis. This is commonly observed in type I cryoglobulinaemia, where the cryoprecipitate is a homogeneous IgM alone or, rarely, IgG.

Since no evidence of positive hepatic serology was found, we think that HIV infection itself could be the cause of cryoglobulinaemia in our patient. Of interest, type III cryoglobulins are thought to be due to antigen-driven disordered B cell stimulation [6]. This type of disordered B cell stimulation occurs conmonly in HIV disease [7]. In addition, Le Lostec et al. [3] found that symptoms and serum cryoglobulins disappeared two months after begining antiretroviral therapy with zidovudine, and propose it as the first-line treatment for symptomatic cryoglobulinaemia in HIV-infected patients. We think that HIV infection could now be added to the list of infectious agents associated with type III cryoglobulinaemia. The optimum treatment for these patients remains to be determined.

REFERENCES

1. Taillan B, Garnier G, Pesce A. Cryoglobulinaemia related to hepatitis C virus infection in patients with human immunodeficiency virus infection. Clin Exp Rheumatol 1993; 11: 350.

2. Stricker RB, Sanders KA, Owen WF. Mononeuritis multiplex associated with cryoglobulinaemia in HIV infection. Neurology 1992; 42: 2013-5.

3. Le Lostec Z, Fegueux S, Vitale C, Geoffroy O, Bleton F, Mornet P. Peripheral neuropathy associated with cryoglobulinaemia but not related to hepatitis C virus in an HIV-infected patient (letter). AIDS 1994; 8: 1351-2.

4. Gaffuri L, Repetto L, Rossi E, Oliva C, Rosso R, Rizzo F. Haemolytic anaemia with positive cryoglobulin test in a HIV positive man (letter). Eur J Cancer 1991; 27: 304.

5. Muñoz-Pérez MA, Rodriguez-Pichardo A, Camacho F, Colmenero MA. Dermatologic findings correlated with CD4 lymphocytes counts in a prospective 3 year study of 1,161 patients with HIV disease predominantly acquired through intravenous drug abuse. Br J Dermatol 1998 (in press).

6. D'Amico JB, Colsanti G, Ferrario F, Sinico RA. Renal involvement in essential mixed cryoglobulinaemia. Kidney Int 1989; 35: 1004-14.

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