Amicrobial pustulosis of the folds. Report of 6 cases and a literature review.

BACKGROUND: Amicrobial pustulosis of the folds (APF) is a rare entity characterized by relapsing pustular lesions involving mainly the cutaneous folds. The disease typically occurs in the context of an autoimmune disorder and is classified within the spectrum of neutrophilic dermatoses. OBJECTIVE: We studied 6 young females having APF associated with various autoimmune diseases or with the presence of serum autoantibodies and reviewed the literature, in order to give a clinical overview on this syndrome. METHODS: Various routine and immunological laboratory tests, histopathological examination as well as direct and indirect immunofluorescence examinations were performed. In vitro neutrophil function was evaluated in 5 cases. We report our findings and compare our cases with those published in the literature. RESULTS: Clinically, at least one major fold and at least one minor fold as well as the anogenital area were always involved. We documented an impaired neutrophil chemotaxis in 2 subjects, neutrophil dysfunction, thus failing to be a verifying criterion. CONCLUSION: APF is a neutrophilic dermatosis affecting young females, which usually shows a benign clinical behavior. Although systemic corticosteroids are the most widely used therapeutic agents, we suggest that the combination of cimetidine and ascorbic acid represents a safe alternative, which may induce long-lasting clinical remission.

Unusual variants of non-Langerhans cell histiocytoses.

Histiocytic syndromes represent a large, heterogeneous group of diseases resulting from proliferation of histiocytes. In addition to the classic variants, the subset of non-Langerhans cell histiocytoses comprises rare entities that have more recently been described. These last include both forms that affect only the skin or the skin and mucous membranes, and usually show a benign clinical behavior, and forms involving also internal organs, which may follow an aggressive course. The goal of this review is to outline the clinical, histologic, and ultrastructural features and the course, prognosis, and management of these unusual histiocytic syndromes.

Treatment of refractory pemphigus with the anti-CD20 monoclonal antibody (rituximab).

BACKGROUND: Pemphigus is a severe blistering disorder caused by autoantibodies to desmogleins 1 and 3. Because some patients with pemphigus never enter into remission, new immunosuppressants are warranted. Rituximab is a chimeric monoclonal antibody binding to the CD20 antigen on B cells, which proved to be effective in recalcitrant pemphigus. OBJECTIVES: To evaluate the efficacy and safety of rituximab in refractory pemphigus and to investigate its effects on the autoantibody profile. PATIENTS AND METHODS: Six patients with recalcitrant pemphigus were treated. Rituximab was administered intravenously at a dosage of 375 mg/m2 body surface once weekly for 4 weeks. RESULTS: Three pemphigus foliaceus patients and 1 with mucocutaneous pemphigus vulgaris (PV) showed complete response over a follow-up period of up to 18 months. In one oral PV, control of the disease was achieved using pulse therapy with cyclophosphamide following rituximab withdrawal. In one PV with vegetating features, good improvement was obtained after 6 rituximab infusions. All patients tolerated the treatment well. Anti-desmoglein autoantibodies significantly decreased only in pemphigus foliaceus. CONCLUSIONS: This study highlights that rituximab is a valuable drug for refractory pemphigus, although the response of mucous membranes and cutaneous folds may be delayed.

Widespread porokeratotic eccrine ostial and dermal duct nevus along Blaschko lines.

Porokeratotic eccrine ostial and dermal duct nevus is a congenital hamartoma of possible eccrine origin with no malignant potential. It is usually localized at the extremity of a single limb, while wider systematized distribution has rarely been documented. A child with an unusually widespread nevus following Blaschko lines is reported. The disorder had a striking presentation in the form of a systematized linear epidermal nevus composed of multiple tiny filiform keratotic spines, which histologically corresponded to columns of porokeratosis. Serial histopathologic sections of a 4-mm punch biopsy specimen barely demonstrated an anatomic relationship between the porokeratotic columns and the underlying acrosyringeal duct. This report provides further evidence of porokeratotic eccrine ostial and dermal duct nevus being distributed along Blaschko lines, thus confirming it is a peculiar epidermal nevus due to a mosaic cutaneous condition.

Wells syndrome in adults and children: a report of 19 cases.

BACKGROUND: Wells syndrome, an uncommon inflammatory dermatosis, is characterized by protean cutaneous manifestations, suggestive but not specific histopathologic findings, and usually a recurrent course. Because of its original description as a distinct entity, it has come to be regarded as an abnormal eosinophilic response to a number of causative agents. OBSERVATIONS: The medical records of 19 patients (12 adults and 7 children) with Wells syndrome referred to the Institute of Dermatological Sciences from 1990 to 2005 were evaluated for the type and prevalence of skin lesions, clinical course and response to treatment, and possibly associated systemic symptoms, as well as histologic, laboratory, and immunofluorescence findings. The classic plaque-type variant proved to be the most common presentation in children but not in adults, who more frequently had the annular granuloma-like variant. Unilesional forms were found to occur more frequently in children. The course was recurrent, although slowly progressing, with a mean duration of disease of 5 years for adults and 3 years for children. CONCLUSIONS: We emphasize the concept that the diagnosis of Wells syndrome is a clinicopathologic diagnosis. Although it should be classified within a spectrum that includes multisystem eosinophilic disorders, such as Churg-Strauss and hypereosinophilic syndromes, Wells syndrome, which has 7 variants, is a distinct cutaneous disease lacking systemic involvement.

Juvenile gangrenous vasculitis of the scrotum: Is it a variant of pyoderma gangrenosum?

Juvenile gangrenous vasculitis of the scrotum was described by Piñol et al in 1974 as a unique variant of scrotal gangrene of unknown origin, occurring exclusively in young individuals. It was characterized by an acute onset of skin ulcers undergoing complete resolution after appropriate therapy, with no relapses. We present a typical case of this extremely rare disease affecting a 16-year-old boy in whom the scrotal ulcerations were preceded by an episode of pharyngitis with fever. The condition promptly regressed after administration of intramuscular betamethasone in combination with oral ciprofloxacin. According to Piñol et al, juvenile gangrenous vasculitis of the scrotum, although poorly known to dermatologists, should be regarded as a distinctive entity within the wide group of scrotal gangrenes. On the other hand, the hypothesis that this condition may well represent a variant of pyoderma gangrenosum is discussed.

Reticular erythematous mucinosis occurring in a brother and sister.

Reticular erythematous mucinosis (REM) is a rare, primary cutaneous mucinosis clinically characterized by a persistent reticular erythema on the mid chest and mid-upper back, and histologically by a mononuclear cell infiltrate and deposits of mucin in the dermis. To our knowledge, the present report of REM occurring in a Caucasian man and his sister is the first reported case of familial REM. Since a host-specific immune response to unknown antigens may be involved in the pathogenesis of this entity, human leukocyte antigen typing was determined and compared to those reported in autoimmune diseases.

Short contact therapy with tazarotene in psoriasis vulgaris.

BACKGROUND: We present the results of a multicentre, not controlled, clinical study on the tolerability and efficacy of tazarotene gel, used as short contact therapy (SCT), in psoriasis vulgaris. OBJECTIVE: To evaluate whether irritant contact dermatitis caused by tazarotene was less frequent and/or less severe with SCT than with traditional therapy, and whether SCT with tazarotene was as effective as traditional therapy. METHODS: Forty-three patients with plaque psoriasis were treated by SCT with 0.1% tazarotene gel (once daily application for 20 min, followed by washing with water). Treatment duration was 45 days. RESULTS: Irritant contact dermatitis caused by tazarotene used as SCT was much less frequent and severe than traditional treatment with the same drug. SCT with tazarotene was effective in the treatment of plaque psoriasis. CONCLUSION: Tazarotene, used as SCT, was better tolerated than the same drug used as traditional treatment. Furthermore, SCT appeared to be as effective as traditional therapy with the same drug.

Treatment of refractory blistering autoimmune diseases with mycophenolic acid.

BACKGROUND: Immunosuppressive drugs are used as steroid-sparing agents in the management of blistering autoimmune diseases. Mycophenolic acid (MPA) is a relatively new adjuvant drug that selectively inhibits T and B lymphocyte proliferation by suppressing de novo purine synthesis. OBJECTIVE: To evaluate the efficacy of MPA in refractory blistering autoimmune diseases and the safety profile of a recent formulation, enteric-coated mycophenolate sodium (EC-MPS), in comparison with mycophenolate mofetil (MMF). PATIENTS AND METHODS: Twelve patients with various bullous dermatoses (three pemphigus vulgaris, one pemphigus herpetiformis, three bullous pemphigoid (BP), two cicatricial pemphigoid (CP) and three epidermolysis bullosa acquisita (EBA)) were enrolled in the study. In 10 cases, MPA was administered in combination with systemic corticosteroids, while in two patients with severe diabetes mellitus MPA was employed as monotherapy. The total time on MPA varied from 2 to 8 months. Four patients were given MMF (2,000 mg daily), seven received EC-MPS (1,440 mg daily) and one received both sequentially. RESULTS: Complete remission, lasting for a mean time of 6.1 months, was achieved in 10 patients. Partial remission was obtained in two patients with disseminated CP and EBA. Both MMF and EC-MPS were well tolerated, but the latter was better in terms of gastrointestinal adverse effects. CONCLUSIONS: MPA may be proposed as a first-line adjuvant agent for pemphigus as well as for refractory BP and CP. MPA monotherapy has to be considered in selected cases of BP and pemphigus. The highly promising results obtained in EBA suggest a future key role for MPA in the management of this disease.

Fatal CD8+ epidermotropic cytotoxic primary cutaneous T-cell lymphoma with multiorgan involvement.

A 70-year-old woman presented with a 3-month history of two ulcerated erythematous-violaceous nodular lesions over the nose and forehead, respectively. The patient's history included a similar cutaneous nodule on the glabella diagnosed as pseudolymphoma 2 years ago. At that time, despite the diagnosis of a benign disease, an adequate staging was performed, ruling out any extracutaneous involvement. During hospitalization, multiple purpuric papules developed over the abdomen, and the disease spread to mediastinal lymph nodes, lungs and the central nervous system. Based on the histologic, immunophenotypic and molecular biology findings, a diagnosis of CD8+ epidermotropic cytotoxic primary cutaneous T-cell lymphoma was made. Secondary skin involvement by a CD8+ extracutaneous T-cell lymphoma could not be excluded with certainty, but seemed to be unlikely because of the negativity of the initial workup. The patient died from complications of right femoral artery thrombosis before starting specific polychemotherapy 21 months after onset of the disease. Among primary cutaneous T-cell lymphomas, the CD8+ epidermotropic cytotoxic subset comprises rare, highly aggressive forms characterized by metastatic spread to unusual sites such as the oral cavity, lungs, testis and the central nervous system but usually not to the lymph nodes. These cases seem to be distinct from mycosis fungoides with CD8+ phenotype, which shows a nonaggressive clinical behavior.

Juvenile xanthogranuloma associated with neurofibromatosis 1: 14 patients without evidence of hematologic malignancies.

The clinical features and natural history of juvenile xanthogranuloma (JXG) in 14 children affected by neurofibromatosis 1 (NF1) are reported. Mean follow-up in 11 of these patients was 4.3 years (range 1-10 years). None of the children developed hematologic malignancies during this period. The onset of JXG was in the first 2 years of life in 13 of the patients. In this series, the association between JXG and six or more café au lait spots more than 5 mm in diameter was a good marker for NF1 in the first few years of life. Overall the JXG in these patients did not show any features distinguishable from those of "classical" JXG.

Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome.

Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed "KIND1" [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage.

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.

Nitrendipine-induced subacute cutaneous lupus erythematosus.

A 66-year-old man presented with widespread annular and bullous subacute cutaneous lupus erythematosus (SCLE), developed after starting treatment for hypertension with the calcium channel blocker nitrendipine. A few days after withdrawal of the drug, while cutaneous manifestations were improving, left hemiparesis occurred. Laboratory investigations showed, in addition to anti-Ro, anti-La and anti-histone antibodies, the presence of lupus anticoagulant, anticardiolipin antibodies, prolonged APTT and thrombocytopenia. On the basis of the spontaneous regression of the patient's skin lesions after discontinuation of the drug, a possible relationship between nitrendipine intake, the clinical events and the biological findings is discussed.

Papular xanthoma associated with angiokeratoma of Fordyce: considerations on the nosography of this rare non-Langerhans cell histiocytoxanthomatosis.

BACKGROUND: Papular xanthoma (PX) is a rare normolipidemic non-Langerhans cell histiocytoxanthomatosis affecting both children and adults. OBJECTIVE: We describe an adult case of PX associated with angiokeratoma of Fordyce and review the literature in order to compare and discuss previous reports. METHODS: We studied the clinical, histopathological, immunocytochemical and ultrastructural findings. RESULTS: We report the findings of our case and compare our case with those described in the literature. CONCLUSIONS: Three clinical patterns of PX appeared to emerge in the review of the literature: a self-healing form, a persistent form and a progressive form. The progressive form of PX can be considered the same clinical entity that is also described as progressive nodular histiocytosis.

Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children.

OBJECTIVE: Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion. RESULTS: BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously. EFFICACY: Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively). SAFETY: There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months. CONCLUSIONS: Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.