The Combination of Complement Deficiency and Cigarette Smoking as Risk Factor for Cutaneous Lupus Erythematosus in Men; A Focus on Combined C2/C4 Deficiency

P. Boeckler; M. Milea; A. Meyer; B. Uring-Lambert; E. Heid, G. Hauptmann; B. Cribier; D. Lipsker


The British Journal of Dermatology. 2005;152(2):265-270. 

In This Article


The clinical and biological characteristics of the 85 patients with CLE are summarized in Table 1 . There were 48 females and 37 males (F/M ratio = 1·3), with a mean age of 41 years at diagnosis. The mean duration of the disease was 34 months. Seventy-three percent of patients had chronic CLE, namely DLE (41%), generalized DLE (26%) and lupus panniculitis (6%); 27% had SCLE. Only 9% of the patients had four or more ARA criteria of SLE. Fifty-two percent of the patients were photosensitive, mainly patients with SCLE (80%) and male patients with generalized DLE (77%). The great majority (82%) of the patients smoked cigarettes. This was especially true in males: 94% were smokers compared with 69% of females.

In this retrospective series, 32 patients with CLE were screened for a complement deficiency; 23 patients were screened on a systematic basis, being referred by one of the authors who is interested in complement deficiency (D.L.) and who is screening systematically all patients with CLE for C4 and C2 deficiency. Nine patients with CLE were screened because they had diminished CH50 and/or C4 levels without any sign suggestive of systemic involvement that could indicate complement consumption. Among the remaining 53 patients, eight had diminished C4 levels, clearly related to complement consumption in two of them.

A complement deficiency was present in 24 patients. Among them, 17 patients had a C4A deficiency, five a C4B deficiency and two a combined partial C2 and C4A deficiency. One patient had a complete C4AQ0Q0 deficiency and two patients had a complete C4BQ0Q0 deficiency. All other patients had partial C4A or C4B deficiencies. The serum level of C4 was decreased in 42% of the patients with a C4A deficiency and in 20% of the patients with a C4B deficiency. The CH50 level was decreased in 40% of patients with C4B deficiency and in only 5% of patients with C4A deficiency. The C3 level was normal in all patients. A high proportion (58%) of these complement-deficient patients were male (F/M ratio = 0·70); the mean age at diagnosis was 36 years.

A brief description of the two patients with a combined C2 and C4 deficiency follows.

A 34-year-old caucasian man, with a history of smoking 40 cigarettes per day, was referred to us for sun-exposed erythematous and oedematous, sometimes annular skin lesions (Fig. 1). Vanishing lesions resulted in grey and telangiectatic maculae without significant atrophy. A biopsy was consistent with the diagnosis of LE and direct immunofluorescence studies revealed a lupus band with a dust-like particle pattern. Otherwise, examination was unremarkable.

A patient with a combined C2 C4 deficiency and annular lesions of subacute cutaneous lupus erythematosus.

Immunological studies revealed the presence of antinuclear antibodies at a titre of 1/640 with anti-Ro(SSA) specificity. CH50 and C3 were in the normal range, but C4 and C2 were decreased at 0·13 g L—1 and 8·3 mg L—1, respectively. A partial C4A deficiency was seen upon C4 phenotyping (C4A4AQ0B2B1) and it pointed to an associated C2 type I deficiency which could be proven by PCR analysis, showing a 28-bp deletion in the C2 gene. HLA phenotyping showed that he had the combination of the HLA-A*01, B*08, DRB1*10, DQB1*05 and A*25, B*18, DRB1*15, DQB1*06 alleles transmitted together with the BF*S allele. He reported only a minor response to antimalarials, retinoids and dapsone, but poor compliance was suspected.

His 32-year-old sister was also investigated and found to have the same complement deficiency. However, until now she has no clinical evidence of an autoimmune disorder.

A 25-year-old male patient had erythematous and keratotic plaques on the face and the back evolving into atrophic and dyschromic lesions (Fig. 2). A cutaneous biopsy showed the typical findings of LE and direct immunofluorescence studies revealed a lupus band. He had no clinical or biological signs of systemic involvement. The C3 level was in the normal range. CH50 was at the lower limit of normal (35 U mL—1). C4 and C2 levels were decreased at 0·14 g L—1 and 8·9 mg L—1, respectively. Heterozygous C4A deficiency was seen upon C4 typing (C4A4AQ0B2B2 phenotype) and heterozygous type I C2 deficiency was confirmed by PCR analysis. He had the combination of HLA-A*28, B*18, DRB1*15, DQB1*06 and HLA-A*02, B*40, DRB1*13, DQB1*06 alleles transmitted together with the BF*S allele. He had good response to antimalarials and topical steroids.

Erythematosus and keratotic lesions in a patient with a combined C2 C4 deficiency and disseminated discoid lupus erythematosus.


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