Lupus erythematosus in children: A report of six casesDermatology Department, Habib Thameur Hospital, Tunis.
Samy Fenniche MD, Sana Triki MD, Rym Benmously MD, Hayet Marrak, MD Feiza Ben Ammar MD, Insaf Mokhtar MD
Dermatology Online Journal 11 (2): 11
The clinical features of childhood discoid lupus erythematosus (DLE) are similar to those of adult DLE in presentation and chronic course. However, children have a particularly high levelS of transition to systemic disease. Systemic lupus erythematosus (SLE) is the most common rheumatic disease associated with significant morbidity and mortality in children. This is a retrospective study reporting all cases of childhood lupus erythematosus observed in the dermatology department of Habib Thameur Hospital over a 14-year period. From 1989 to 2003, six cases of childhood lupus erythematosus are included, three patients with discoid lupus erythematosus (2 girls, 1 boy), and three patients with systemic lupus erythematosus (2 boys, 1 girl). The mean age of onset was 12 years (range 10-16 years). Skin manifestations were localized in sun exposed areas in both discoid and systemic lupus erythematosus. Photosensitivity was noted in all cases. The diagnosis was confirmed by histopathologic examination, direct immunofluorescence, and immunologic findings. Treatment included sun avoidance, oral hydroxychloroquine, and topical and systemic steroids. An average follow-up time was 18.1 months (1-96 months). The severity of onset of SLE is usually greater in children than adults. We note that lupus erythematosus is not a static disease and progression from DLE to SLE is possible.
Discoid lupus erythematosus (DLE) is uncommon in childhood, especially during the first 2 years of life . Several authors suggest the presence of DLE in children is associated with less severe disease, milder renal disease, and a more benign course . However, other authors note a higher frequency of transition from DLE to systemic lupus erythematosus (SLE) in children compared to adults .
Nearly 15 percent of SLE presents in children younger than age 16 . Recent reports comparing adult and pediatric onset SLE suggest that the presenting features are more severe in children than adults . We performed a retrospective analysis of the clinical features of childhood SLE and DLE in our clinic population in Tunis.
All cases of childhood DLE and SLE observed in the dermatology department of Habib Thameur hospital were included in this study from 1989 to 2003.
The diagnosis of discoid lupus erythematosus was made on the basis of clinical findings and confirmed by histopathologic examination or immunofluorescence studies. The diagnosis of SLE was made only when at least 4 of the preliminary criteria established by the American Rheumatism Association (ARA) were present. The following data were recorded: sex, age at the onset, age at the time of diagnosis, family history of DLE and SLE, clinical characteristics, location and number of lesions, laboratory tests, histopathological findings, and progression or not of DLE toward SLE. The follow up was from 1 to 5 months after disease onset for discoid lupus erythematosus and from 2 months to 8 years after disease onset for systemic lupus erythematosus.
Six patients with a clinical and histopathologic diagnosis of lupus erythematosus were included in the study. The mean age of onset was 12.5 years (range 10-15 years) with all cases occurring after age 10. No family history of LE was noted. One child had chronic anemia and celiac disease.
|Figure 1||Figure 2|
|Figure 1. Discoid plaque of the cheek.|
|Figure 2. Discoid atrophic plaque of the nose.|
|Figure 3||Figure 4|
|Figure 3. Malar rash in a boy with systemic lupus erythematosus.|
|Figure 4. Erythematous plaques of the face in a girl with systemic lupus erythematosus.|
Among the six patients, three (2 girls and 1 boy) had discoid lupus erythematosus (Figs. 1 and 2). Lesions were localized initially on the face in three patients, subsequently disseminating to the neck and thorax in one case. Erythema, scaling, hyperpigmentation and atrophy were the predominant cutaneous lesions. Direct immunofluorescence (DIF) was performed in two patients and was positive in one case showing a lupus band by the presence of immunoglobulin G, IgM, IgA, and C3 complement at the epidermodermal junction. The histopathological examination showed epidermal atrophy, hyperkeratosis and follicular dilatation with keratin plugging and liquefactive degeneration of the basal layer of the epidermis. A dense perivascular and periappendageal mononuclear cell infiltrate was predominant in the dermis. No clinical or laboratory evidence of systemic disease was found during the short period of follow up. Sunscreens were routinely used by three patients. Topical corticosteroids were prescribed to one patient. Systemic treatment, comprising hydroxychloroquine (5 mg/kg/day), was given to two patients. The therapeutic response was considered satisfactory in the three patients after 1 month of treatment.
|Digital necrosis in systemic lupus erythematosus.|
Three children with systemic lupus erythematosus were seen at the same period of study (2 boys and 1 girl). Arthritis, arthralgias, rash (Figs. 3 and 4), and Raynaud phenomenon were the commonest presenting symptoms. One patient developed hemolytic anaemia, lupus nephritis, fever, digital necrosis (Fig. 5), pleurisy and pericarditis. All the patients had a raised erythrocyte sediment rate. Direct immunofluorescence (DIF) was performed in two patients using involved and uninvolved skin and was positive in both. The histopathology of the cutaneous lesions showed a basal cell hydropic degeneration, a papillary dermal edema and a mild perivascular inflammatory cell infiltrate. Antinuclear antibody (ANA) and antinative DNA were positive in two cases. Decreased complement level was observed in two cases. Positive anti-ENA was present in one case. Treatment included hydroxychloroquine and systemic corticosteroids. Patients were also advised to avoid sun exposure. All three patients were referred to the medecine department. The evolution was considered satisfactory after 4 months of followup. The clinical features and evolution are summarized in Table 1.
Discoid lupus erythematosus is a rare disorder in childhood . Only 74 cases of pediatric DLE have been reported in the English literature. A statistical analysis of 1579 patients seen over 2 years in a pediatric dermatology clinic revealed only one case of childhood discoid lupus erythematosus . As observed in our 3 cases, less than 2 percent of patients with discoid lupus erythematosus have an onset before age 10. A female predominance is generally noted in childhood as it if for adults [7, 8].
There were 2 previous tunisian studies of childhood DLE. In 1998 Mokhtar et al. reported  a series of nine children with discoid lupus erythematosus with a female predominance (7 female : 2 male). In 2003 Cherif et al.  reported a series of 16 cases of childhood DLE and noted a sex ratio of 1 (8 female : 8 male).
The most common clinical features in childhood DLE are discoid plaques (characterized by scarring, atrophy, follicular plugging, and scale) and photosensitivity. Cutaneous lesions are usually localized in sun exposed areas.
Recently, linear lesions have been described .
The diagnosis can be confirmed by histopathologic and direct immunofluorescent examination of skin biopsy specimens of an active lesion. Our patients had histopathologic features similar to those reported in adults, except there is less epidermal atrophy [12, 13]. The progression from localized DLE to widespread DLE seems to be a harbinger of the development of SLE . The extent of cutaneous lesions did not seem to correlate with the development of SLE [3, 15]. However, some authors suggest that patients who develop SLE have widespread cutaneous disease, early age of onset, long evolution, and treatment unresponsiveness [3, 17]. Other authors note that DLE starting in children less than 10 years of age has a similar risk of progression to SLE as DLE of more than 10 years of age . In our three patients, discoid lesions progressed from the face to the neck and thorax in one case (patient 1), no change in the laboratory findings and no onset of systemic features have been detected. However, the follow-up of our patients was too short to predict the clinical course. Long term follow up is necessary for SLE screening in children with DLE.
Treatment of DLE should be individualized and adjusted to the disease activity. Patients should be advised to use broad-spectrum sunscreen and to avoid excessive sun exposure. If these strategies do not lead to regression, hydroxychloroquine (4-6mg/kg/day) or the combination of antimalarial agents and prednisolone (1-3mg/kg/day) can be administrated to rapidly control the disease [3, 8]. SLE occurs in adult and pediatric populations, with nearly 15 percent of cases present in children younger than age 16. As reported by Caeiro, fewer than 26 percent of patients with SLE have an onset before age 10 . Major organ system involvement in childhood SLE is similar to that found in adults. However, the frequency and severity appear to be increased in children and adolescents [4, 16]. General clinical features in childhood SLE include broad variations between presence of rash, arthritis, constitutional symptoms, renal disease, cardiovascular, pulmonary, and neuropsychiatric involvement . Comparing the clinical features of childhood-onset and adult onset disease reveals similarities and important differences. The frequency of skin, joint and central nervous system disease was similar in both groups, and correlates with previous reports [18, 19, 20, 21]. However, renal involvement appears to be more common and more severe in children and adolescents, with estimates of prevalence raging from 50 to 80 percent of all patients. Adult-onset patients had more frequent cardiovascular manifestations, whereas childhood-onset patients had more frequent hematological manifestations . The most common cardiac manifestation in childhood SLE is pericarditis (24 %), as seen in our patient. The number of children with SLE manifesting coronary heart disease is unknown, but there are reports of myocardial infarctions in children with SLE . The process of atherosclerosis begins before symptoms manifest and most likely originates in the pediatric years, even in healthy children .
The incidence of pulmonary involvement in children with SLE varies from 5 to 67 percent depending on the study . The most common pulmonary features in children include pleuritis (as seen in our patient), acute pneumonitis, chronic interstitial lung disease, pulmonary fibrosis, alveolar hemorrhage, respiratory and diaphragm myopathy, and pulmonary hypertension. Neuropsychiatric manifestations, reported in 29-44 percent of pediatric patients with SLE  were not found in our patients. The most common neurologic symptoms in children include headaches, coma, psychosis and depression. Mucocutaneous manifestations in children with SLE include rash (76 %), photosensitivity (28 %), alopecia (55 %), Raynaud phenomenon (31 %), vasculitis (54 %), oral ulcers (19 %), purpura (16 %) and discoid lesions (7 %) . In our cases, we noted photosensitivity, rash, and Raynaud phenomenon in two cases and digital vasculitis in one case. Comparison of the auto-antibody profiles of adult and childhood-onset cases reveals a higher frequency of elevated anti-DNA antibodies in children . Some authors suggest that the presence of anti-DNA antibodies may relate to the higher frequency of renal disease in the children . In our study, we noted the presence of anti-DNA antibodies in 2 cases. Some authors have shown a higher mortality for children during the first year after diagnosis , while others have shown an even distribution of mortality over the first 5 years . Infection associated with active disease is the main cause of death and renal failure the second most frequent. The complexity of this chronic illness in children and its effects on normal physical and psychosocial development, in addition to frequent severe organ system damage, make SLE a high priority for development of new tools for diagnosis and evaluation, and the development of new approaches to understanding the etiopathogenesis.
Advances in the treatment of SLE have significantly decreased renal organ damage and mortality. The use of corticosteroids in combination with intravenous pulse cyclophosphamide has been shown to be the most effective regimen in preventing progression of severe lupus nephritis in adults and children . However, there is a lack of responsiveness of the skin lesions to systemic corticosteroids in patients with SLE.
In conclusion, lupus erythematosus is less often observed in children than adults. It is important to note that lupus erythematosus is not a static disease and progression from DLE to SLE is possible. The clinicians should be aware of the greater risk of systemic complications in children with systemic lupus erythematosus between 2 and 5 years of disease onset. Therefore, patients with DLE and SLE should be continually followed up and therapy modified in response to the patient clinical course and disease activity.
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