Association between the clinical and histopathological classifications of actinic keratosis and the efficacy of topical imiquimod treatment.

We investigated the association between the clinical and histopathological classifications of actinic keratosis (AK) and the efficacy of topical imiquimod treatment. Forty patients (55 lesions) with AK were treated with topical 5% imiquimod and the efficacy of imiquimod for AK was evaluated based on the clinical/histopathological changes. The complete remission (CR) rates in patients with the different clinical classifications of AK were 85.4% (erythematous type) and 46.2% (hyperkeratotic type). The CR rates in the different histopathological classifications of AK were 80% (hypertrophic type), 81.8% (atrophic type) and 42.9% (bowenoid type). The results revealed that determining the clinical and histopathological type of AK was important for selecting a therapeutic method. The topical imiquimod treatment could be expected to be more effective for AK clinically classified as the erythematous type, or histopathologically classified as the atrophic or hypertrophic type. However, it would be expected to be less effective for the treatment of AK clinically classified as the hyperkeratotic type or histopathologically classified as the bowenoid type. Our observations suggest that we can predict the efficacy of topical imiquimod therapy in AK by determining its clinical and histopathological type.

X-linked dominant protoporphyria: The first reported Japanese case.

A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin derivatives, which revealed a markedly elevated level of erythrocyte protoporphyrin (EP) and a diagnosis of EPP was made. The patient's mother had no photosensitivity, however, lesions appearing slightly as small scars were found on the dorsum of her right hand; his elder sister and father showed no rash. The EP levels were elevated in samples from his mother and mildly elevated in those from his elder sister and father. To obtain a definitive diagnosis, genetic analyses were performed using samples from all family members, which revealed no mutations in the ferrochelatase-encoding gene (FECH), which is responsible for EPP. Instead, a pathological mutation of the 5-aminolevulinic acid synthase-encoding gene (ALAS2) was identified in samples from the patient, his mother and his elder sister, confirming a definitive diagnosis of X-linked dominant protoporphyria (XLDPP). This is the first Japanese family reported to have XLDPP, demonstrating evidence of the condition in Japan. In addition, because XLDPP is very similar to EPP in its clinical aspects and laboratory findings, a genetic analysis is required for the differential diagnosis.

Dermatomyositis as a complication of interferon-α therapy: a case report and review of the literature.

Autoimmune disorder is one of the important side effects of interferon-α therapy. Some polymyositis cases as complication of interferon-α therapy were reported, but dermatomyositis were rarely. We report a case of dermatomyositis as a complication of interferon-α therapy for hepatitis C. A 52-year-old Japanese man was treated by combination therapy with pegylated interferon-α-2b and ribavirin for hepatitis C. Three months after the initiation of therapy, he showed erythema in the posterior cervical to dorsal and anterior cervical to thoracic regions, weight loss, general malaise, muscle pain, and severe increase in levels of muscle enzymes. We made a diagnosis of dermatomyositis according to these clinical features, proximal muscle-predominant myogenic change on electromyography, and infiltration of monocytes and CD4+-dominant lymphocytes on skin biopsy, although myositis-associated antibodies were absent. He was successfully treated with intravenous immunoglobulin and tacrolimus in addition to glucocorticoid. This is a very rare case of dermatomyositis associated with interferon-α therapy. We reviewed several similar published cases and the association of dermatomyositis and type I interferon.

Immunohistochemical analysis of O(6)-methylguanine-DNA methyltransferase in human melanoma in comparison with skin squamous cell carcinoma.

Alkylating agents, often used for chemotherapy in patients with melanoma, can produce O(6)-alkylguanine (O(6)AG) which is related to tumor cell killing after treatment with alkylating agents. O(6)AG is effectively eliminated by O(6)-methylguanine-DNA methyltransferase (O(6)MGMT) and its level is correlative to the resistance to alkylating agents. However, little is known about the relationship of O(6)MGMT to the characteristics of melanoma. This study investigated the expression of O(6)MGMT in 12 melanomas and compared it with that in 11 skin squamous cell cancers (SCCs) immunohistochemically to evaluate the O(6)MGMT activity in melanoma and its clinical significance. All of the SCC samples had high O(6)MGMT expression, while the expression of O(6)MGMT in melanoma was diverse and 4 out of 12 samples had no or extremely low O(6)MGMT activity. Out of 6 lesions obtained from metastasis, 4 had a high O(6)MGMT activity. Two out of 3 cases with a low O(6)MGMT activity in each primary lesion did not show any evidence of metastasis or local recurrence. The evaluation of O(6)MGMT activity in melanoma may, therefore, be useful to determine the characteristics of tumor in each melanoma case. In addition, the present study implies the possibility of selective cancer chemotherapy for melanoma in the near future.