Immunologic changes in linear scleroderma in children. Apropos of 11 cases

Immunologic data collected in 11 children (6 girls and 3 boys under fourteen) presenting with linear scleroderma were analysed in a retrospective study: 2 children presented with superficial linear scleroderma, 6 with monomelic scleroderma, 1 with dimelic scleroderma, 1 with the "en coup de sabre" variety associated with dimelic homolateral involvement, and another with "en coup de sabre" scleroderma combined with facial hemiatrophy: Antinuclear antibodies (ANA) were demonstrated in 9/11 cases (i. e. 81 p. 100). The immunofluorescence staining pattern was homogeneous in all nine with a low titer (less than 250 in 5 of them). ANA to single stranded DNA was present in 1/3. The demonstration of ANA in these 9 children was correlated with deep or extensive sclerosis with muscular involvement in 7. But neither the presence nor the titer of ANA were correlated with the subsequent development of osteoarticular sequelae. The level of total complement appeared to be lowered in 3/8 cases. No renal involvement was demonstrated. Blood tests for circulating immune complexes were positive in 4/8 patients. Skin biopsy for direct immunofluorescence was performed in 6 children and demonstrated immunoglobulin deposits in 4: three had IgM fixation on the dermo-epidermal junction, and one had speckled fixation of IgG on epidermal nuclei (this has not previously been reported in localized scleroderma). There data highlight: a--the high frequency of ANA in linear scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)     

HLA in systemic scleroderma (PSS) and familial scleroderma

HLA in systemic scleroderma (PSS), including three familial cases, is reported. Three families in which one sister developed PSS and another sister suffered from either PSS (family 1), mixed connective tissue disease (MCTD) (family 2), or Sjögren's syndrome (SjS) (family 3) were described. The elder sister in family 1 died of respiratory insufficiency caused by scleroderma lung. The sisters in family 2 both had SjS, anti SS-A antibodies, and HLA A2-Bw55-Cwl-DRw8 haplotype in common. The elder sister with PSS in family 3 also had SjS and Hashimoto's thyroiditis. HLA in 28 PSS patients including these 3 familial cases were analyzed with 4 MCTD and 4 generalized morphea patients. HLA A2, Bw46, DR2, DRw8, DRw6 and DQw1 antigens were more frequently found in the PSS patients than in the controls. HLA DRw6 was the only antigen that was positive in common in the 3 familial cases. In those patients with anti topoisomerase I antibodies, HLA DR2 antigen was found more frequently than in the controls. Some, but not all, of these results were similar to the previous reports on HLA in PSS. Further investigations on more patients and the other members of these families would be necessary to clarify the significance of these results.     

Nodular (keloidal) scleroderma

Two patients with progressive systemic sclerosis (PSS) developed keloidal-like nodules within areas of thickened skin. This extremely unusual event is most likely a keloidal response to the early inflammatory component of scleroderma in patients who are either genetically at risk for keloid formation or in areas of the skin that have a high predilection for keloid formation such as the chest.     

Localized scleroderma in adults and children. Clinical and laboratory investigations on 239 cases

We examined, retrospectively, 239 patients (113 adults and 126 children) with LS, referred to our department from 1980 up to 2001. Clinical parameters evaluated were age, sex, LS variant, extracutaneous manifestations, duration of disease and follow-up. We also considered laboratory findings, most notably erythrocyte sedimentation rate, blood eosinophilia, antinuclear antibodies (ANA) and various circulating autoantibodies. Plaque morphea was the most common form in both groups (74 adults and 61 children). In contrast, linear scleroderma affected children much more frequently than adults (22 children vs 7 adults). When the limbs were involved, this variant could lead to severe orthopedic complications (10 children vs one adult patient). On the other hand, linear scleroderma of the scalp and face comprising scleroderma en coup de sabre and Parry-Romberg syndrome was also more frequent in children (14 children vs 5 adults) causing ocular (8 cases), oral (7 cases) and neurologic (8 cases) abnormalities. Typical of childhood were mixed forms (18 pediatric patients), characterized by combination of different LS variants, which usually followed a more protracted and complicated course and showed ANA positivity (11 cases). Among adults, Raynaud's phenomenon was found in 8 patients; interestingly, anticentromere antibodies were detected in 4 of these subjects, identifying a subset at risk for progression to systemic disease. Children and adults developed LS with analogous clinical and immunological features. However, the prevalence of LS variants differed between adult and pediatric populations, leading to different extracutaneous complications.     

Linear IgA bullous dermatosis in tunisian children: 31 cases

Background:

Linear IgA bullous dermatosis (LAD) of children is relatively frequent in Africa.

Aim:

We undertook this study to evaluate the frequency of this disease among autoimmune bullous diseases (AIBDs) in Tunisian children.

Materials and Methods:

We present a 32-year retrospective study (January 1976 to December 2007). Children with chronic acquired bullous diseases seen at the Charles Nicolle Hospital of Tunis and for who direct immunofluorescence (DIF) of the perilesional skin demonstrated linear IgA immunoglobulin deposits were included in the study population.

Results:

Thirty-one children with LAD were selected representing 65.9% of all AIBDs of children selected in the same period, with a mean age of 5.5 years and a sex ratio (M/F) of 2.4. Most of the children had generalized eruption (28/31), more profuse on the face, pelvic region, buttocks and limbs. Mucosal lesions happened in only four children (12.9%). The mean duration of the disease was 14 months. DIF demonstrated linear IgA deposits along the dermal–epidermal junction in all patients. IgG, IgM, and complement were also seen (20/31). Indirect immunofluorescence was negative in 67% of cases. Eight patients responded to dapsone; however, prednisone had to be added in seven children to control the disease and erythromycin in four others. A long-term remission period was achieved in 76.1% of patients.

Conclusion:

This study confirms that LAD is the most common AIBD in children in Tunisia which frequently occurs in preschool-aged males. Independently of the used drug, a long-term remission is frequently observed.     

Systemic scleroderma in children. Apropos of 5 cases. A review of the literature

Systemic scleroderma is a rare disease in childhood. 62 cases are analyzed. Cutaneous manifestations are identical to those seen in adults. However Raynaud phenomenon is much more frequently missing but follow-up of patients is only of 4 years' duration. We want to draw attention on possible worsening of clinical signs during intercurrent infectious episodes. We report exceptional roentgenological bone anomalies. Gastro-intestinal tract is frequently involved, particularly the oesophagus. We want to draw attention on latent small intestine involvement. A normal thoracic X-ray examination cannot rule out involvement of the lungs; systematic respiratory functional tests are absolutely necessary. All parts of the cardiac wall can be involved: we underline the particular seriousness of this involvement as it was exclusively responsible of death in 10 cases out of 21. Renal involvement is rare. We are reporting 2 cases where a staturo-ponderal retardation remains unexplained; 7 other cases in the literature report on isolated weight retardation. Biological anomalies are similar to those reported in adult. Treatment is not well-codified; we can hope that a better understanding of the disease's physiopathology will lead to the discovery of an efficient therapy.     

Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children

BACKGROUND: Localized scleroderma (LS) or morphoea is often considered to be a benign self-limiting condition confined to the skin and subcutaneous tissue. However, the course of the disease is unpredictable and severe functional and cosmetic disability may result. Drug treatment with systemic corticosteroids in combination with methotrexate has been reported to be beneficial in LS, but data in children is limited. OBJECTIVES: To evaluate the efficacy and tolerability of systemic corticosteroids in combination with methotrexate in children with LS. METHODS: Treatment and outcome of 34 patients with LS were retrospectively analysed. Pulsed intravenous methylprednisolone was given, followed by oral prednisolone on a reducing regimen and maintenance treatment with methotrexate. We assessed treatment outcome clinically and by thermography and monitored adverse events. RESULTS: From the onset of treatment, the disease stopped progressing in 94% of the patients. All patients demonstrated significant clinical improvement within a mean time of 5.7 +/- 3.9 months. Mean duration of follow-up over the treatment period and beyond was 2.9 +/- 2.0 years. In 16 (47%) patients therapy was discontinued when the disease was considered to be inactive clinically; however, seven (44%) of the 16 developed a relapse, necessitating repeat treatment. At last follow-up (range 0.2-7.0 years), 24 (71%) of the 34 patients had completely inactive disease. Observed adverse events were moderate and transient and no patient had to stop therapy. CONCLUSIONS: These data suggest that systemic corticosteroids and methotrexate in combination are beneficial and well tolerated in the treatment of children with LS. Because of the risk of relapse after discontinuing therapy, long-term monitoring is mandatory.     

Treatment of linear scleroderma with oral 1,25-dihydroxyvitamin D3 (calcitriol) in seven children

Linear scleroderma is a connective tissue disorder that characteristically involves the skin. Skin induration and pigmentary changes present in a linear distribution. Severe functional and cosmetic disability may occur, especially in growing children. No effective therapy for the fibrotic stage of scleroderma is available at present. Recently a beneficial effect of oral 1, 25-dihydroxyvitamin D3 (calcitriol) treatment was reported in adults. Calcitriol has a dose-dependent inhibition on fibroblast proliferation and collagen synthesis and has immunoregulatory activities. We assessed the efficacy of oral calcitriol treatment in seven pediatric patients with linear scleroderma. During the treatment dietary calcium intake was restricted. Calcium, inorganic phosphate, creatinine, and urea in the serum and urine was monitored. The urinary calcium:creatinine ratio was measured. The effects of the treatment were evaluated using a clinical scoring system. No side effects were observed. Five of the seven patients showed a good to excellent improvement of their lesions. One of them partly relapsed after 19 months, but showed an excellent response to a second therapy session with calcitriol. One patient with rapidly progressive disease failed to respond to therapy. Our results indicate that calcitriol can be an effective agent for treating localized scleroderma in children.