[Sclerosing tufted angioma. Apropos of 4 cases involving lower limbs]. / Angiome en touffes sclérosant. A propos de 4 observations aux membres inférieurs.

BACKGROUND: Tufted angioma belongs to the family of vascular skin proliferations. Clustered capillaries is the characteristic histological feature. Classically, tufted angioma is an acquired disease observed in children or young adults with lesions predominating on the neck, the shoulders and the upper trunk. CASE REPORTS: Four children were seen for flat skin lesions which were either initially or secondarily erythematous. The lesions were observed at birth or within the first weeks of life. In all 4 cases, the lesions progressed by infiltration, leading to sclerous plaques within a few weeks. The hip area was involved in case n(o) 2 and the thigh in the other cases. Pathology reported tufted angioma. A repeated biopsy 4 years after the first biopsy demonstrated the progressive nature of the fibrosis in case n(o) 2. Magnetic resonance imaging, performed in 3 of the 4 cases, demonstrated deep penetration of the vascular proliferation. The lesions were in contact with bony structures in case n(o) 2, reached the hypodermis in case n(o) 3 and infiltrated between the adducter muscles in case n(o) 4. DISCUSSION: Among tufted angiomas, there is a clinical variant characterized by very early discovery (congenital or within the first months of life), preferential localization on the lower limbs and progression to sclerosis. Although non-specific, hypersudation and lanuginous hypertrichosis are also highly suggestive signs. The main clinical and histological differential diagnosis is angio-eccrine hamartoma and, to a lesser degree, Kaposi hemangioendothelioma which does not predominate on the lower limbs. This particular clinical presentation of tufted angioma should lead to wide and sufficiently deep biopsy to allow precise diagnosis prior to initiating therapy. The possibility of spontaneous involution would allow abstention with regular surveillance to detect reactivation and progression or functional impairment. Such unfavorable progression has lead certain authors to propose high-dose systemic corticosteroid therapy or alpha-interferon.

[Enoxaparin-induced cutaneous necrosis localized on insulin lipodystrophies]. / Nécroses cutanées à l'enoxaparine localisées sur des zones de lipodystrophie insulinique.

INTRODUCTION: Low-molecular weight heparin-induced cutaneous necrosis is exceptional. Pathogenesis remains unclear. We report an exceptional case with elective localization of the necrotic areas in insulin lipodystrophic tissue. CASE REPORT: A 69-year old patient developed areas of skin necrosis after starting enoxaparin therapy. These areas were located far from the points of injection and focalized on skin areas where the patient had been injecting insulin daily for the last four years. These areas had an aspect of insulin lipodystrophy. Biopsy specimens showed leukocytoclastic vasculitis. There were no associated biological anomalies. One month later, prick-tests were made with different low-molecular weight heparins and calcium heparinate in a lipodystrophic area together with an enoxaparin control test in healthy skin. The only positive test was for enoxaparin in an insulin lipodystrophic area (hard erythema at 24 hours). Histology at 72 hours demonstrated leukocytoclastic vasculitis. DISCUSSION: Six cases of cutaneous necrosis induced by low-molecular weight heparin have been reported, including three cases with enoxaparin. Two pathophysiological mechanisms could be involved: (i) localized heparin-dependent platelet aggregation, or (ii) vasculitis induced by type III hypersensitivity reaction. In our case, the leukocytoclastic aspect of the vasculitis was compatible with an immune complex hypersensitivity reaction. The localization of the necrotic areas would be explained by enoxaparin-induced preferential deposit of immune complexes in the vascular turbulences present in lipodystrophic areas.

[Treatment of discoid lupus erythematosus with sulfasalazine: 11 cases]. / Traitement du lupus érythémateux chronique par la sulfasalazine: 11 observations.

INTRODUCTION: Antimalaria agents and thalidomide are two reference drugs for discoid lupus erythematosus. In non-responders or after secondary resistance or contraindications, there are a number of alternative therapeutics which are less effective and more toxic. We therefore conducted an open study in patients with discoid lupus erythematosus treated with sulfasalazine. PATIENTS AND METHODS: Seven men and four women (mean age 40 years) with severe discoid lupus erythematosus (mean duration of disease 14 years) were treated with sulfasalazine (2 g/d). This treatment was initiated after a previous failure or contraindication of antimalarial drugs or thalidomide. The acetylation phenotype was predicted in all patients with N-acetyltransferase 2 genotyping. Genome DNA was tested for mutations causing an N-acetyltransferase deficiency. Homozygous individuals or those with heterozygous composites for the tested mutations were predicted slow acetylators and those with a homozygous or heterozygous genotype for an allele carrying a normal sequence at the mutation sites were predicted rapid acetylators. RESULTS: We had 7 complete responses, 1 partial response and 3 failures. Mean delay to efficacy was 7 weeks, longer for lesions involving the scalp (4 to 5 months). Six of the 8 responders were given sulfasalazine exclusively. The effect was suspensive and dose-dependent; the minimal effective dose was 1.5 g/d. Excepting light sensitization requiring discontinuation, there were no clinically significant side effects. Neutropenia occurred in one patient and moderate and transient live enzyme movements did not require treatment withdrawal. The only immunoallergic side effect (light sensitization) observed occurred in a slow acetylator. All responders except one were rapid acetylators. DISCUSSION: Salazosulfapyridine, or sulfasalazine, is composed of a derivative of 5-aminosalicylic acid and a sulfamide fraction, sulfapyridine. It is only marginally used in dermatology except for psoriasis. Its efficacy in chronic lupus erythematosus has been reported in one case. We confirmed the role of this compound in the treatment of chronic lupus erythematosus. The rare observations of induced lupus and development of antinuclear antibodies are not a contraindication, but require close regular clinical and biological surveillance. The potential risk is that possible hypersensitivity could lead to reserving sulfasalazine for severe resistant chronic lupus erythematosus after failure with antimalarials and thalidomide. Nevertheless, our study demonstrates that the slow acetylator phenotype predicts immunoallergic events, as observed by other authors, and would be a factor predicting nonresponse. If these results are confirmed by other studies, it would be possible to propose sulfasalazine as a treatment for discoid lupus erythematosus in rapid acetylators.

[Perforating milia-like idiopathic calcinosis of the extremities in Down syndrome]. / Calcinose miliaire idiopathique perforante des extrêmités chez une malade trisomique 21.

INTRODUCTION: Several skin diseases can be seen in patients with trisomy 21. We report a case of miliary calcinosis of the extremities. CASE REPORT: A 15-year old adolescent with Down's syndrome presented small papular miliary lesions which had developed over 18 months and tended to discharge a chalk-like substance via the epidermis. Approximately 15 lesions were present on the hands and feet. Histologically, there was a well-delimited calcium deposit in the superficial dermis. There was no alteration in phosphorus/calcium metabolism. Brain CT-scan and cardiac echography did not reveal any calcifications. DISCUSSION: Miliary calcinosis cutis may not be exceptional in Down's syndrome, although only 9 observations have been reported. Preferential localizations include the hands, wrists and feet. Association with syringoma has been noted but would appear to be fortuitous. Transepidermal elimination of the calcium deposits is frequent. Pathogenic hypotheses include precipitation of calcium salts in sudation products and/or increased synthesis by fibroblasts. The association with trisomy 21 appears to be significant since only three cases have been reported in patients with normal karyotypes. This entity should be individualized as perforating milia-like idiopathic calcinosis cutis of the extremities.

[Ofuji's eosinophilic pustular folliculitis. Efficacy of acitretin]. / Folliculite pustuleuse a éosinophiles D'Ofuji Efficacité de l' acitrétineétine.

BACKGROUND: We report the first case of eosinophilic pustular folliculitis (Ofuji's disease) which was successfully treated with acitretin. CASE REPORT: A 50-year old women (HIV negative) had developed over 3 months an erythematopapulous plaque under the left orbit. The clinical and histological diagnosis was eosinophilic pustular folliculitis. Successive treatment with cetirizine then indomethacin was ineffective. Acitretin (0.5 mg/kg/d) was then started and led to cure within 1 month. Six weeks after the patient spontaneously stopped the treatment, the lesion recurred at the same localization. Further treatment with isotretinoin (0.5 mg/kg/d) was then given but did not alter progression of the lesion. Acitretin was then reintroduced at the same dose and again produced rapid cure. Acitretin was then tapered off to 10 mg/d then maintained at this dose as lesions reappeared with further dose reduction. DISCUSSION: It is difficult to treat eosinophilic pustular folliculitis because of the random nature of response to different drugs. General corticosteroids, dapsone and indomethacin are classically proposed but with variable success. Isotretinoin is proposed on the hypothesis of a link with sebaceous secretion, but results have been contradictory. This drug was ineffective in our case. Acitretin did however provide very rapid improvement with an efficacy confirmed at reintroduction. This retinoid which does not have the specific action of isotretinoin could affect follicular keratinocytes which have been shown to be activated in this chronic skin disease.

IgE autoantibodies directed against the major bullous pemphigoid antigen in patients with a severe form of pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized in part by circulating and tissue-bound IgG autoantibodies directed against the basement membrane zone. In addition, most of the patients with BP have increased serum IgE levels which seem to be correlated with the disease activity, whereas the presence of circulating anti-basement membrane zone IgE Abs has been reported in some patients. To elucidate whether IgE-dependent mechanisms play a role in the physiopathology of BP, we looked for the presence of IgE Abs specifically directed against the major BP Ag (BPAg1) in sera of BP patients at the onset and after remission of the disease. A radioimmunoassay and a 55-kDa recombinant protein (rBP55) obtained from a cDNA sequence, encoding the C-terminal region of the BPAg1 and containing the BPAg1 immunodominant epitopes, were used. Anti-rBP55 IgE Abs were found in 12 of the 19 sera tested. When the patients were divided into two groups according to the disease severity, anti-rBP55 IgE Abs were found only in patients with a severe form of the disease. Cytophilic IgE was detected on approximately 20% of peripheral blood eosinophils purified from BP patients. Immunohistochemistry studies suggested that some of the IgE-bearing cells in the lesional skin of BP patients are eosinophils. Immunostaining experiments revealed the existence of FcepsilonRI on both peripheral blood and tissue eosinophils. Taken together, these results suggest that IgE-dependent mechanisms could participate in the constitution of the lesions in BP.

Linear and whorled nevoid hypermelanosis versus incontinentia pigmenti: is pigmentary incontinence really a distinctive feature?

This report describes a 3-year-old boy who presented with skin lesions characterized by multiple streaks of hyperpigmentation following Blaschko's lines since 6 weeks of age. The clinical features are consistent with the diagnosis of linear and whorled nevoid hypermelanosis (LWNH), but differ substantially from this entity by the pigmentary incontinence observed on both the paraffin and electron microscopy sections. Despite the presence of pigmentary incontinence, the diagnosis of incontinentia pigmenti (IP) can be ruled out on the basis that the patient is a male, with none of the characteristic anomalies present in this syndrome, and that he never presented with inflammatory or eruptive skin lesions. This observation suggests that pigmentary incontinence may not differentiate IP from LWNH as conclusively as previously reported in the literature.

Keratoderma with scleroatrophy of the extremities or sclerotylosis (Huriez syndrome): a reappraisal.

Keratoderma with scleroatrophy of the extremities, also referred to as Huriez syndrome, is a rare, autosomal dominant condition, first described in 42 of 132 members of two families from northern France. The term sclerotylosis was proposed because of the pseudosclerodermatous appearance of the hands and digits. The distinctive feature of this syndrome is the risk of the development of squamous cell carcinoma on affected skin. Since the initial description of this disease, three other families, and possibly a fourth, have been reported. In the present study, we reassessed the clinical, pathological and genetic data in 114 members of one of the two original families, of whom 27 were affected by this syndrome.

[Mycoplasma infection with Stevens-Johnson syndrome and antiphospholipid antibodies: apropos of 2 cases]. / Infection à mycoplasme avec syndrome de Stevens-Johnson et anticorps antiphospholipides: à propos de deux cas.

We report two cases of Mycoplasma pneumoniae infections associated with Stevens-Johnson syndrome and antiphospholipid antibodies. Such an association has been noted once in the literature. The relationship between antiphospholipid antibodies and Stevens-Johnson syndrome and others cutaneous manifestations of infections diseases is discussed. Though mainly described in systemic lupus erythematosus and autoimmune diseases, anticardiolipin antibodies and lupus anticoagulant have been found in many infectious disorders. But in the latter conditions, they have been considered by many authors as "non pathogenic" or "non prothrombotic" on epidemiologic and immunologic data. We suggest that antiphospholipid antibodies could possibly play a role in their pathogenesis especially as the mechanisms are not to date clearly understood.

Dermatomyositis with follicular hyperkeratosis.

We report 2 cases of dermatomyositis with follicular hyperkeratosis (FHK) in children. They occurred in a 10-year-old Vietnamese girl and a 9-year-old Caucasian boy. The girl's FHK disappeared after 2 months of treatment. The boy presented, 15 months after the onset of his dermatomyositis, with a generalised FHK which lasted for 6 months. FHK can appear before, during or after dermatomyositis. It is more often generalized but can be localised. Erector pili myositis and ostial hyperkeratosis may be the explanation. The prognostic value of FHK in dermatomyositis is unknown. This manifestation, initially considered to be more frequent in the Far East, is not as rare in Western countries as the few reported cases suggest.

[Pemphigoid mimicking epidermolysis bullosa acquisita]. / Pemphigoide simulant une épidermolyse bulleuse acquise.

INTRODUCTION: Subepidermal autoimmune bullous dermatoses form a clinical entity for which there is not always an individualized clinical and pathological description. CASE REPORT: A patient presented with bullous skin disease of atypical nature. There was an almost total desepidermization of the legs, vast areas of erosion on the trunk and arms with a Nikolski sign in an area of healthy skin, buccal involvement, multiple milium cysts and ungueal dystrophies with nail loss. DISCUSSION: This clinical presentation in this patient suggested acquired bullous epidermolysis. However, according to the recently defined clinical criteria for pemphigoid, the probability of correct diagnosis of pemphigoid was greater than 95 p. 100 since nearly three fourths of the major criteria were present. This diagnosis was confirmed by reference techniques (electron microscopy, indirect electron immunomicroscopy and immunoblotting). Thus, bullous autoimmune diseases of the dermoepidermal junction can be reliably differentiated on the bases of the clinical features, together with direct and indirect immunofluorescence on salt-split skin.

[Hamartomatous dysplasias with hemihypertrophy. 2 cases including one with Proteus syndrome]. / Dysplasies hamartomateuses avec hémihypertrophie. Deux observations dont un syndrome Protée.

BACKGROUND: Hamartomatous dysplasias with hemihypertrophy are a part of several congenital diseases, sometimes difficult to classify when their symptomatology is relatively poor. CASE REPORTS: Case 1. A girl, 11 year-old, suffered from gigantism of the feet, left hemihypertrophy of the limbs, scoliosis and kyphosis. X-rays showed frontal hyperostose, bony and soft tissues overgrowth involving the left limbs and pelvis with hip dislocation and coxa valga. The vertebrae were hypertrophic and dysplastic. No tumor could be found. Case 2. A girl, 18 year-old, suffered from left hemihypertrophy of limbs and face associated with homolateral cutaneous hemangioma. X-rays showed enlargement of bone and soft tissue. No tumor or venous abnormalities were observed. CONCLUSION: A diagnosis of Proteus syndrome was made in the first patient while the second patient was considered to have Klippel-Trenaunay syndrome even though hemangiomatous involvement has been seen in Proteus syndrome.

[Cutaneous pseudolymphoma during treatment of rheumatoid polyarthritis with low-dose methotrexate]. / Pseudolymphome cutané au cours du traitement d'une polyarthrite rhumatoïde par le méthotrexate à faibles doses.

INTRODUCTION: Over the last three years, there have been over twenty case reports of lymphoma in patients given low-dose methotrexate for rheumatoid arthritis. We observed the first case of cutaneous pseudolymphoma. CASE REPORT: A 56-year-old man had been treated with methotrexate (15 mg/day) for 6 years due to rheumatoid arthritis. He developed three isolated papulonodular ulcerations on the limbs. The histology and immunohistochemical examinations demonstrated T and B lymphoplasmocyte infiltration without epidermotropism nor destruction of the annexes. Immunolabelling for anti-Epstein-Barr virus was negative. There was a IgG lambda type monoclonal hypergammaglobulinaemia, Bence-Jones proteinuria and an increase in beta 2-microglobulin. The thoracoabdominal scan, bone marrow biopsy and gallium scintigraphy were normal. There was no sign of a Gougerot-Sjögren syndrome nor of a Felty syndrome. The skin lesions and the Bence-Jones proteinuria disappeared rapidly after withdrawal of methotrexate. There has been no recurrence with a follow-up of 16 months. DISCUSSION: The diagnosis of pseudolymphoma was retained on the basis of the clinical features, the histological and immunohistochemical evidence and especially on the clinical course after methotrexate withdrawal, i.e. spontaneous regression of the lesions within 3 weeks. A similar course has been observed in three cases of lymphocyte proliferation suggesting that this immunosuppressor would be the most probable causative agent. Lymphocyte proliferation, mainly B-cell lymphomas in haematopoietic organs occurring under methotrexate administration have occurred mainly in patients with rheumatoid arthritis. Three cases have also been described in patients with dermatomyositis, but none have been reported in patients with psoriasis. This would suggest that cofactors involved in these autoimmune diseases could also have an effect: immunodepression, potentialization due to associated treatment (corticosteroids), Epstein-Barr virus... CONCLUSION: Data on these observations should be combined in order to analyse the question of the safety of low-dose methotrexate in these patients.