Discoid lupus erythematosus developing in areas where fragments of windshield glass had become embedded in the skin

ARTICLE

Lupus erythematosus has a wide spectrum of clinical manifestations, from cutaneous discoid lupus erythematosus (DLE) to systemic lupus erythematosus (SLE), which affects different organs and tissues. Various autoantibodies and immunopathies have been studied, but the etiology and the pathology of lupus erythematosus have not been fully elucidated. Factors such as fatigue, stress, sunlight, trauma and drugs have been shown to cause or exacerbate lupus erythematosus (LE). In this paper, we report a case of discoid lupus erythematosus that we suspect was caused by fine fragments of windshield glass having become embedded in the skin in an automobile accident.

Case report

We observed a 26-year-old female patient who had a patchy infiltrated erythematous lesion only on the skin of her left cheek. According to her history, in December 1984, when she was 18 years old, she was in an automobile accident and fine fragments of windshield glass became embedded in the left side of her face. Subsequently, she underwent three operations for removal of the fragments at a general hospital (Fig. 1).

Approximately two years prior to the initial visit (June 1992), the patient began to experience stiffness in her fingers in the morning. Then, starting in the later part of last year, edematous erythematous patches became noticeable in the scarred areas on the left side of her face. In addition, the border of these erythematous patches became gradually demarcated, and signs indicative of infiltration were observed.

When she visited us initially, she complained of slight general fatigue, malaise and morning stiffness of the fingers. In the skin, several infiltrating erythematous patches with defined borders were seen only on the left side of her face, matching the scars caused by the automobile accident and the operations. Keratotic scales had formed on the surface of these patches, and pigmentation was noticed (Fig. 2). The keratotic areas were painful to scratch. Erythema was not detectable on the right side of her face where she did not have any injury or scar. ltching, slight fever, arthralgia and Raynaud's syndrome were not confirmed.

Clinical laboratory tests showed the following results ; peripheral leukocyte count (WBC): 4,900/mm³, erythrocyte count (RBC): 420 x 10⁴/mm³, urinalysis: normal, erythrocyte sedimentation rate: 19 mm/hour, total serum protein: 8.0 g/dl, fasting blood sugar 87 mg/dl, A/G ratio: 1.35, serum albumin: 4.6 g/dl, globulin: 3.47 g/dl, alkaline phosphatase: 451 U/l, GPT: 131 U/l, GOT: 81 U/l, BUN: 12 mg/dl, UA: 3.0 mg/dl, anti-nuclear antibody: x 320, the antibodies against RNP,SS-A/Ro,SS-B/La, cardiolipin: all negative, rheumatoid factor(Rf): negative, serum CH₅₀: 47 U/ml.

Biopsy specimens of the affected areas (Figs. 3 and 4) showed atrophy of the epidermal layer, liquefaction degeneration of the basal cell layer, keratotic plug formation, patchy infiltration of lymphocytes around blood vessels and hair follicles, and cicatricial hyperplasia of collagen bundles in the middle to deep layers of the dermis, accompanied by infiltration of lymphocytes and histiocytes. In some areas, degeneration of collagen bundles and histiocytes mimicking foreign body granuloma were densely surrounded by infiltrating lymphocytes. Although fragments of windshield glass were not detected under the microscope, focal tissue cracks were seen in different areas of the skin. There were no specific changes in the subcutaneous fat tissue. Signs associated with epithelioid granuloma, indicating cutaneous tuberculosis or sarcoidosis, were not seen. Also, signs suggesting malignant lymphoma were not detected.

The granular deposits of lgG and C3 were confirmed in the dermo-epidermal basal membrane zone of the affected areas by immunofluorescent staining.

Based on the results of clinical observations, histological and immunohistological analyses and clinical laboratory tests, we ruled out sarcoidosis, malignant lymphoma, cutaneous tuberculosis, foreign body granuloma. Finally the patient was diagnosed as having discoid lupus erythematosus. However, since the patient tested positive to anti-nuclear antibodies and her erythrocyte sedimentation rate was slightly elevated, DLE may advance to SLE in the future. The patient had no family or past history suggesting rheumatic or collagen diseases.

As therapy, starting on June 8, 1994, 50 mg/day of diaphenylsulfone (DDS) was administered orally. Approximately one month later, erythema and infiltration had improved significantly. On October 4, 1994, the levels of peripheral leukocyte count (2,900/mm³) and erythrocyte count (339 x 10⁴/mm³) decreased, thus the DDS administration was discontinued. Since her condition had somewhat deteriorated, 15 mg/day of prednisolone was administered instead, and the patient is currently healthy and the affected area of the left side of her face is only pigmented without any infiltration. In August 2000, her local and general conditions were symptom free, however serum ANF remains still positive and the titer increased to x 640. The antibodies against RNP, SSA, SSB and cardiolipin were still negative and serum CH50 was 41.7. The peripheral WBC count was 4,703/mm³.

Discussion

DLE is a subset of lupus erythematosus. Although the patient was diagnosed as having DLE, the fact that she tested positive to anti-nuclear antibodies and had a slightly elevated erythrocyte sedimentation rate, general malaise and morning stiffness of the fingers suggests the possibility of DLE progressing to SLE in the future. The most interesting clinical feature in the present case was that prior to the development of lupus erythematosus, numerous fine fragments of windshield glass had become embedded in the patient's face skin during an automobile accident. In this patient, lupus erythematosus became apparent about eight years after the accident, only in areas where fine pieces of windshield glass were buried. She underwent three operations to remove these fragments after the accident. Pictures that were taken during these operations were made available to us. We contacted the attending surgeon at the time of the accident. According to his judgement, it is highly possible that minute amounts of windshield glass still remain in her face.

Histological analysis showed typical findings compatible with those of DLE, surrounded with foreign body granulomas and patchy lympho-histiocytic infiltrations in cicatricial tissues rich in collagen. The main component of the windshield glass is a kind of amorphous quartz, which is melted at a higher temperature and such a melted quartz consists of silica or SiO₂, which can also induce inflammation [1]. Silica acts as an adjuvant, and long exposure over several years to silica by the respiratory route can induce silicosis. Silicosis patients in some cases have rheumatoid arthritis (Caplan syndrome) or other collagen diseases (systemic scleroderma, SLE, dermatomyositis or Sjogren's syndrome) [2-5]. Intracutaneously embedded silica can occasionally cause silica-granuloma directly in the skin (Murphy) [6] and be carried into regional lymphnodes (Kuchemann) [7].

We recently reported silicosis patients who were complicated by pemphigus vulgaris or pemphigoid and who tested positive for specific autoantibodies [8, 9], suggesting that persistent silicosis brings about systemic immunological abnormalities which induce autoimmune diseases.

Although the precise mechanism by which silica activates histiocytes and lymphocytes is not clear, it is highly probable that histiocytes engulfing silica release IL-1. Also, it has been reported that silica acts as a super-antigen for lymphocytes in the presence of macrophages in in vitro study [10], and also provocates activation-induced cell death in human lymphocytes [11]. In addition, the soluble Fas antigen and decoy receptor 3 gene are increased in the patients with silicosis [12, 13].

Thus, normal apoptosis of T lymphocytes may be reduced in these patients.

The relationship between silica as a super-antigen and events such as production of autoantibodies and the onset of collagen diseases or autoimmune diseases, needs to be investigated in the future. In in vitro study, silica also can induce several inflammatory cytokines, collagenase and adhesion molecules [14, 15]. Although the pathogenic significance of these inflammatory agents remains unknown, some potential relationship to Koebner phenomenon should be speculated.

In addition, some unknown genetic factors might play an important role in the induction of autoimmune disease in such patients.

Based on the above findings, we speculated that the present patient may have a certain genetic characteristic, and that persistent exposure to silica may have caused immunological abnormalities. To the best of our knowledge, there is no documented case in which discoid lupus erythematosus developed in areas where glass or silica is embedded in the skin.

Since the present patient tested positive for anti-nuclear antibodies, her condition may deteriorate in the future.

In the present case, the use of an anti-inflammatory agent temporarily improved the patient's condition. However, as fine glass particles are likely to still be present in the skin of her cheek, immunological abnormalities and DLE may gradually develop. Thus, we are planning to continue to treat and follow this patient closely.

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