A kindred with familial progressive hyperpigmentation-like disorder: implication of fibroblast-derived growth factors in pigmentation.

Two patients with a generalized, progressive dyschromatosis disorder are described and investigated as a model to study the role of fibroblast-derived mediators on skin pigmentation. The patients (father and daughter) had had a widespread hyperpigmentation since early life which then progressively worsened with the appearance of hyperpigmented macules, café-au-lait macules and freckles, also involving the lips, palms and soles, intermixed with small hypopigmented spots. These features resembled those of familial progressive hyperpigmentation (FPH). Histology revealed a normal epidermis with pronounced keratinocyte hyperpigmentation and the presence of dermal melanophages. Ultrastructural analysis showed basal and suprabasal keratinocytes enriched in melanosome complexes. Immunohistochemical staining displayed an increased expression of hepatocyte growth factor (HGF), stem cell factor (SCF) and keratinocyte growth factor (KGF) in fibroblast-like cells of the upper dermis in hyperpigmented lesions of both patients, compared to control healthy skin. Our data suggest that a persistent activation of fibroblasts abnormally stimulating melanocyte functions is involved in hyperpigmentation disorders.

Effective management of psoriasis symptom worsening during efalizumab therapy without discontinuing treatment: a case study.

Efalizumab is an effective therapy for the long-term treatment of chronic plaque psoriasis. However, regardless of the type of antipsoriatic treatment a patient is receiving, natural fluctuations in symptom severity occur throughout the course of the disease, and need to be managed appropriately. Here, we report the case of a patient with moderate chronic plaque psoriasis resistant to conventional treatments, who initially showed an excellent response to efalizumab (1 mg/kg per week, subcutaneous injection), but then experienced symptom exacerbation after 8 weeks of treatment. This worsening of symptoms was successfully controlled using a short course of concomitant methotrexate treatment (15 mg/week, intramuscular injection). After 1 month, the clinical signs had cleared, methotrexate treatment was stopped and efalizumab therapy was continued. These results show the effective use of a short course of concomitant methotrexate to control fluctuations in psoriasis severity in a patient receiving efalizumab therapy in general clinical practice.