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A blistering rash and swollen knees
Case report
A blistering rash and swollen knees M B Hogarth, T Qureshi, J Lloyd, R G Rees In December, 1997, a 36-year-old woman was admitted to hospital with a non-itchy, blistering rash on her legs and buttocks, which had been present for 4 weeks. This rash was associated with pain and swelling of her knees and ankles. She had no other symptoms. 8 weeks previously she had had an episode of fever and night sweats for 1 week. There was no associated sore throat, respiratorytract infection, or diarrhoea. She had not taken any medications apart from amoxycillin and codeine, which had been started 5 days before admission. She had no previous history of recurrent infection. There were no risk factors for HIV-1 infection. She had a family history of diabetes and Crohn’s disease. On examination she was apyrexial, and had a purpuric rash with bullae (figure). There was synovitis of the knees and ankles but no detectable effusion. Investigations showed haemoglobin 11·5 g/dL; white blood cells 9·73109/L (neutrophils 6·0, lymphocytes 2·8); platelets 4503109/L; erythrocyte sedimentation rate 40 mm/h; C-reactive protein 22 mg/L; creatinine 81 mmol/L; random blood glucose 5·4 mmol/L; liver function tests normal; 24 h urinary protein 0·18 g; standard autoantibody screen negative; IgG, IgM, and IgA concentrations normal; increased a2 globulin on electrophoresis; and chest radiograph normal. Microbiological investigations were negative apart from elevated IgM and IgG antibodies to cytomegalovirus (CMV) indicative of a CMV primary infection, 8 weeks previously. A skin biopsy specimen showed leucocytoclastic vasculitis. There were no owl’s eye inclusions. Immunohistochemistry and electron microscopy were negative for CMV, herpes simplex virus, and varicella zoster virus. Immunofluorescence revealed granular fluorescence of C3 in papillary dermal vessel walls. There was no notable fluorescence with IgG, IgA, or IgM. She was started on 40 mg prednisolone daily. The rash resolved with scarring and the steroids were gradually withdrawn over 6 months. IgM antibodies to CMV were undetectable at this time. It is now a year since her initial presentation and she remains immunocompetent. She has had no opportunistic infection or AIDS-defining illnesses and her lymphocyte count remains normal. She was well when last seen in January, 1999. CMV leucocytoclastic vasculitis is well described in immunocompromised patients, in whom the vasculitis is accompanied by owl’s eye intranuclear inclusions indicative of direct infection.1 There have been two previous reports of cutaneous leucocytoclastic vasculitis occurring in healthy children, one in a 7-year-old girl2 and one in a 4-month-old baby.3 In both cases there were no owl’s eye intranuclear inclusions. This suggests that in Lancet 1999; 353: 978 Rheumatology Unit (M B Hogarth MRCP, T Qureshi MB, R G Rees FRCP) and Department of Histopathology (J Lloyd MB ), St Mary’s Hospital, London W2 1NY, UK Correspondence to: Dr M B Hogarth
978
The patient’s legs
immunocompetent patients, the vasculitis is a result of immune-mediated mechanisms rather than direct infection as supported by the granular immunofluorescence of C3 in our patient. In a review of 101 cases of histologically proven cutaneous leucocytoclastic vasculitis, no cause was identified in 26%.4 Infection was implicated in 12%; responsible pathogens including streptococcus, staphylococcus, Escherichia coli, and echovirus. It is unclear whether CMV infection was excluded in any of these cases. We reviewed 37 consecutive cases of biopsy-proven cutaneous leucocytoclastic vasculitis, presenting to St Mary’s Hospital, London, between Jan 1, 1989, and June 30, 1998. None of the biopsy specimens had owl’s eye intranuclear inclusions. CMV antibody titres were measured in only five (13·5%). All of these had elevated IgG but undetectable IgM antibodies to CMV, indicative of previous rather than acute infection. Urine culture for CMV was requested in two patients (5%). In both cases no organism was identified. These findings suggest that CMV infection is not routinely screened for in our hospital in the investigation of cutaneous leucocytoclastic vasculitis. This fact has important implications, particularly for immunocompromised patients, for whom prompt treatment with gancyclovir may be life-saving. In such patients, development of a vasculitic rash may be attributed to the primary illness and immunosuppression increased with disastrous consequences.5 We advocate screening for CMV infection in any patient presenting with cutaneous leucocytoclastic vasculitis. References 1
Golden MP, Hammer SM, Wanke CA, Albrecht MA. Cytomegalovirus vasculitis: case reports and review of the literature. Medicine (Baltimore) 1994; 73: 246–55. 2 Weigand DA, Walter HC, Burgdorf MD, Tarpay MM. Vasculitis in cytomegalovirus infection. Arch Dermatol 1980; 116: 1174–76. 3 Sandler A, Snedeker JD. Cytomegalovirus infection in an infant presenting with cutaneous vasculitis. Pediatr Infect Dis J 1987; 6: 422–23. 4 Sanchez NP, Van Hale HM, Su D. Clinical and histopathological spectrum of necrotizing vasculitis: report of findings in 101 cases. Arch Dermatol 1985; 121: 220–24. 5 Bulpitt KJ, Brahn E. Systemic lupus erythematosus and concurrent cytomegalovirus vasculitis: diagnosis by antemortem skin biopsy. J Rheumatol 1989; 16: 677–80.
THE LANCET • Vol 353 • March 20, 1999
A blistering rash and swollen knees M B Hogarth, T Qureshi, J Lloyd, R G Rees In December, 1997, a 36-year-old woman was admitted to hospital with a non-itchy, blistering rash on her legs and buttocks, which had been present for 4 weeks. This rash was associated with pain and swelling of her knees and ankles. She had no other symptoms. 8 weeks previously she had had an episode of fever and night sweats for 1 week. There was no associated sore throat, respiratorytract infection, or diarrhoea. She had not taken any medications apart from amoxycillin and codeine, which had been started 5 days before admission. She had no previous history of recurrent infection. There were no risk factors for HIV-1 infection. She had a family history of diabetes and Crohn’s disease. On examination she was apyrexial, and had a purpuric rash with bullae (figure). There was synovitis of the knees and ankles but no detectable effusion. Investigations showed haemoglobin 11·5 g/dL; white blood cells 9·73109/L (neutrophils 6·0, lymphocytes 2·8); platelets 4503109/L; erythrocyte sedimentation rate 40 mm/h; C-reactive protein 22 mg/L; creatinine 81 mmol/L; random blood glucose 5·4 mmol/L; liver function tests normal; 24 h urinary protein 0·18 g; standard autoantibody screen negative; IgG, IgM, and IgA concentrations normal; increased a2 globulin on electrophoresis; and chest radiograph normal. Microbiological investigations were negative apart from elevated IgM and IgG antibodies to cytomegalovirus (CMV) indicative of a CMV primary infection, 8 weeks previously. A skin biopsy specimen showed leucocytoclastic vasculitis. There were no owl’s eye inclusions. Immunohistochemistry and electron microscopy were negative for CMV, herpes simplex virus, and varicella zoster virus. Immunofluorescence revealed granular fluorescence of C3 in papillary dermal vessel walls. There was no notable fluorescence with IgG, IgA, or IgM. She was started on 40 mg prednisolone daily. The rash resolved with scarring and the steroids were gradually withdrawn over 6 months. IgM antibodies to CMV were undetectable at this time. It is now a year since her initial presentation and she remains immunocompetent. She has had no opportunistic infection or AIDS-defining illnesses and her lymphocyte count remains normal. She was well when last seen in January, 1999. CMV leucocytoclastic vasculitis is well described in immunocompromised patients, in whom the vasculitis is accompanied by owl’s eye intranuclear inclusions indicative of direct infection.1 There have been two previous reports of cutaneous leucocytoclastic vasculitis occurring in healthy children, one in a 7-year-old girl2 and one in a 4-month-old baby.3 In both cases there were no owl’s eye intranuclear inclusions. This suggests that in Lancet 1999; 353: 978 Rheumatology Unit (M B Hogarth MRCP, T Qureshi MB, R G Rees FRCP) and Department of Histopathology (J Lloyd MB ), St Mary’s Hospital, London W2 1NY, UK Correspondence to: Dr M B Hogarth
978
The patient’s legs
immunocompetent patients, the vasculitis is a result of immune-mediated mechanisms rather than direct infection as supported by the granular immunofluorescence of C3 in our patient. In a review of 101 cases of histologically proven cutaneous leucocytoclastic vasculitis, no cause was identified in 26%.4 Infection was implicated in 12%; responsible pathogens including streptococcus, staphylococcus, Escherichia coli, and echovirus. It is unclear whether CMV infection was excluded in any of these cases. We reviewed 37 consecutive cases of biopsy-proven cutaneous leucocytoclastic vasculitis, presenting to St Mary’s Hospital, London, between Jan 1, 1989, and June 30, 1998. None of the biopsy specimens had owl’s eye intranuclear inclusions. CMV antibody titres were measured in only five (13·5%). All of these had elevated IgG but undetectable IgM antibodies to CMV, indicative of previous rather than acute infection. Urine culture for CMV was requested in two patients (5%). In both cases no organism was identified. These findings suggest that CMV infection is not routinely screened for in our hospital in the investigation of cutaneous leucocytoclastic vasculitis. This fact has important implications, particularly for immunocompromised patients, for whom prompt treatment with gancyclovir may be life-saving. In such patients, development of a vasculitic rash may be attributed to the primary illness and immunosuppression increased with disastrous consequences.5 We advocate screening for CMV infection in any patient presenting with cutaneous leucocytoclastic vasculitis. References 1
Golden MP, Hammer SM, Wanke CA, Albrecht MA. Cytomegalovirus vasculitis: case reports and review of the literature. Medicine (Baltimore) 1994; 73: 246–55. 2 Weigand DA, Walter HC, Burgdorf MD, Tarpay MM. Vasculitis in cytomegalovirus infection. Arch Dermatol 1980; 116: 1174–76. 3 Sandler A, Snedeker JD. Cytomegalovirus infection in an infant presenting with cutaneous vasculitis. Pediatr Infect Dis J 1987; 6: 422–23. 4 Sanchez NP, Van Hale HM, Su D. Clinical and histopathological spectrum of necrotizing vasculitis: report of findings in 101 cases. Arch Dermatol 1985; 121: 220–24. 5 Bulpitt KJ, Brahn E. Systemic lupus erythematosus and concurrent cytomegalovirus vasculitis: diagnosis by antemortem skin biopsy. J Rheumatol 1989; 16: 677–80.
THE LANCET • Vol 353 • March 20, 1999