tacrolimus and Dermatitis--Exfoliative

Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report on a 2-year-old girl presenting with pustular lakes within areas of erythema and large accumulations of intraepidermal neutrophils, which initially led to our misdiagnosis of generalized pustular psoriasis. No mutation was found in either the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations of erythroderma with severe itching, hypotrichosis, enamel defects, onychodystrophy, palmoplantar keratoderma and the crucial result of de novo missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions significantly improved after a 4-week treatment with oral acitretin and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 4 months, relieving her skin pruritus and suggesting that early treatment with pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may even inhibit multiple allergies induced by skin barrier injury. In this work we also review the clinical features, differential diagnoses and pathological manifestations of SAM-DSP syndrome.

Topics: Acitretin; Administration, Cutaneous; Administration, Oral; Child, Preschool; Dermatitis, Exfoliative; Desmoplakins; Diagnosis, Differential; Diagnostic Errors; DNA Mutational Analysis; Female; Gabapentin; Humans; Hypersensitivity; Mutation, Missense; Psoriasis; Severity of Illness Index; Skin; Syndrome; Tacrolimus; Treatment Outcome; Wasting Syndrome

Chronic actinic dermatitis (CAD) is a recurrent photosensitive dermatitis that occurs predominantly on sun-exposed areas with unknown etiology. In severe cases, it may present with erythroderma, which is clinicopathologically analogous to cutaneous T-cell lymphoma. Typically, inflammatory infiltrates in the skin lesions are mainly CD8. Twenty patients with CAD ranging in age from 45 to 86 years (median, 64), including 17 males and three females (M/F ratio, 5.7), were examined. All patients were phototested for UV light. In addition, seven of the 20 patients with extensive eruption were also tested for visible light. All biopsy specimens were obtained from the CAD eruptions (n = 25 lesions). Histopathologic and immunohistochemical studies were performed. Furthermore, flow cytometric analysis was performed to determine the CD4/8 ratio using peripheral blood mononuclear cells of 13 of the 20 patients.. In 11 of the 20 patients (55%), the eruption was localized to sun-exposed areas. Skin-infiltrating T cells were CD8-dominant in the CAD eruption. Three patients (15%) showed erythroderma with a reduced CD4/8 ratio (median, 0.7) of peripheral mononuclear cells. As for treatment, eight of the 20 patients (40%) required oral cyclosporine in addition to topical therapies. Subsequently, the reduced CD4/8 ratio was normalized after treatment in two of the three patients with erythroderma.. We considered that there appeared to be a relationship between the reduced CD4/8 ratio of circulating T cells (hematologic burden) and the affected area (skin burden).

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged; Aged, 80 and over; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Chronic Disease; Cyclosporine; Dermatitis, Exfoliative; Female; Humans; Immunohistochemistry; Immunosuppressive Agents; Male; Middle Aged; Photosensitivity Disorders; Severity of Illness Index; Sunscreening Agents; Tacrolimus; Ultraviolet Rays

Topics: Administration, Topical; Adult; Dermatitis, Exfoliative; Dermatologic Agents; Female; Hair; Humans; Ichthyosis, Lamellar; Syndrome; Tacrolimus

Omenn syndrome is a severe combined immunodeficiency with features of generalised erythroderma alopecia and evidence of Th2 inflammation (eosinophilia and raised IgE). We describe a differential effect of 2 calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus, with CsA rapidly improving the erythroderma and lymphocytosis but tacrolimus having little effect.

Topics: Alopecia; Bone Marrow Transplantation; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Exfoliative; Female; Hepatomegaly; Humans; Infant, Newborn; Lymphocytosis; Mothers; Severe Combined Immunodeficiency; Syndrome; Tacrolimus; Treatment Failure

To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient.. A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained.. Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma.. Tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases.

Topics: Administration, Topical; Adult; Deltaretrovirus Infections; Dermatitis, Exfoliative; Humans; Leukemia, T-Cell; Male; Ointments; Pruritus; Skin Absorption; Tacrolimus; Time Factors