Dermatomyositis-like eruptions and fasciitis with novel compound heterozygous MEFV mutations: Newly recognized features of a variant of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent febrile attacks and serositis. The diagnosis of FMF has been based on clinical criteria, including frequent symptoms and good response to the treatment with colchicine. Some patients with FMF show skin or muscle manifestations, which may be confused with other cutaneous or muscle disorders. Here we report a female in her 40s with periodic fever, migratory myalgia, dermatomyositis-like dermatitis, arthralgia, pharyngalgia, and lymphadenopathy. The initial clinical differential diagnosis included dermatomyositis, malignant lymphoma, and adult-onset Still's disease. However, the following examinations could not explain her pathological condition with such diseases. In particular, findings from muscle and fascial biopsy demonstrated severe inflammatory cell infiltrate in the fascia, suggesting fasciitis as a possible cause of migratory myalgia. We examined the possibility of autoinflammatory diseases by genetic testing. Accordingly, she was found to have novel compound heterozygous mutations (L110P, E148Q, and P369S) in the MEFV gene. Given her genetic mutations and favorable response to colchicine, she was finally diagnosed as a variant of FMF with myalgia and previously unprecedented skin eruptions.

Topical immunotherapy in combination with anthralin in the treatment of refractory alopecia areata.

BACKGROUND: Treatment is often challenging in patients with alopecia areata. We often try topical immunotherapy to treat alopecia areata in Japan. Anthralin is sometimes used in other countries. OBJECTIVES: The aim of this study was to examine effectiveness of combination therapy with both topical immunotherapy with squaric acid dibutylester or diphenylcyclopropenone and anthralin in the treatment of refractory alopecia areata. METHODS: We treat four patients with refractory alopecia areata by topical immunotherapy and anthralin. Two patients had alopecia areata multilocularis and the other two patients had alopecia totalis. The entire scalp was treated with weekly application of squaric acid dibutylester or diphenylcyclopropenone and daily 0.5% anthralin ointment. Patients were followed up weekly, and adverse effects were recorded. RESULTS: One patient with multifocal patches of alopecia areata got complete hair regrowth at week 30, the other patient with multifocal patches of alopecia areata turned for the worse at week 30 and recovered at week 52. Hair regrowth was not seen in the other two patients with alopecia totalis. Localized pruritis and hyperpigmentation of the scalp were seen in two patients. CONCLUSIONS: To treat alopecia areata unresponsive to topical immunotherapy alone, topical immunotherapy in combination with anthralin is worth a try.

Adult-onset Still's disease presenting with aseptic meningitis as the first symptom in an elderly patient.

•Neutrophilic meningitis is rarely observed in Adult onset Still's disease (AOSD).•AOSD-related meningitis has been observed in the AOSD course of young adults.•An elderly man showed neutrophilic meningitis as a first symptom of AOSD.•First-line therapy with steroid for bacterial meningitis complicated the diagnosis.•Hyperferritinemia led to the correct diagnosis of AOSD and AOSD-related meningitis.

Long-term Side Effects Including Blepharitis Leading to Discontinuation of Ripasudil.

PRECIS: Blepharitis was the most common side effect leading to discontinuation of ripasudil therapy. Prior allergic reactions to other topical glaucoma were found to be a risk factor for ripasudil-induced blepharitis. PURPOSE: To report the incidence proportion of blepharitis and its relating factors due to long-term use of 0.4% riapasudil, a Rho-kinase inhibitor, in glaucoma patients of a clinical setting. PATIENTS AND METHODS: One hundred three eyes of 103 consecutive glaucoma patients who started ripasudil treatment between December 2014 and February 2017 at our institute, and who had a follow-up period of over 6 months were enrolled in this study. Incidence proportion, time required for recovery and risk factors associated with blepharitis and other side effects that led to discontinuation of ripasudil treatment were considered. RESULTS: The most frequently observed side effect was blepharitis (25.2%). The 12- and 24-month discontinuation rate due to blepharitis was 21.1%±8.2% and 34.6%±11.8% (average±SE), respectively (Kaplan-Meier analysis). Most patients recovered from blepharitis symptoms within 4 weeks, but 5 patients required over 8 weeks for recovery. Past history of allergic reactions to other topical glaucoma medication was significantly correlated with the manifestation of blepharitis (Cox proportional hazard model, P<0.007) while age, sex, intraocular pressure reduction rate, number of administered eye drops, history of systemic allergic diseases were not. CONCLUSIONS: Blepharitis was the most common reason for discontinuation of ripasudil treatment. Although most cases were resolved spontaneously, prolonged blepharitis was observed in a few patients. A past history of allergic reaction to other glaucoma medication indicates a higher possibility of blepharitis with ripasudil use and warrants careful administration.

Oral propranolol for infantile hemangiomas beyond the proliferative phase.

Infantile hemangiomas grow rapidly during infancy followed by gradual involution. After involution, residual lesions sometimes remain. Despite the prognosis for eventual involution, infantile hemangiomas often cause great psychosocial morbidity that affects patients and their parents. Oral propranolol usually induces earlier involution and redness reduction in infantile hemangiomas in the proliferative phase. However, to evaluate the effectiveness of oral propranolol for infantile hemangiomas beyond the proliferative phase is difficult because of spontaneous regression. We report five Japanese patients treated with 2 mg/kg per day of oral propranolol for infantile hemangiomas beyond the proliferative phase and compared with three untreated patients. After the oral propranolol treatment for 25 weeks, all the treated patients exhibited earlier color fading than untreated patients. Four patients reached nearly complete resolution. Adverse events occurred in three patients: cold, exanthema subitum and suspected of bronchial asthma, respectively. The propranolol treatment for the patient with suspected of bronchial asthma was suspended for 4 months. Recurrence after termination of treatment was not seen. Oral propranolol (2 mg/kg per day) is a safe and effective treatment for Japanese patients with infantile hemangiomas beyond the proliferative phase.

Prolonged growth of infantile hemangioma after pulsed dye laser and oral propranolol treatment.

Infantile hemangiomas are the most common tumor of childhood and undergo rapid growth during early infancy followed by gradual involution. After involution, residual lesions sometimes remain. Oral propranolol usually induces earlier involution and redness reduction of infantile hemangiomas. However, the optimal treatment duration is unknown and infantile hemangiomas sometimes recur after cessation of treatment. We report three Japanese patients with recurrent infantile hemangiomas on their cheek. These patients were a 1-month-old female baby with a superficial infantile hemangioma, a 3-month-old female baby with a mixed infantile hemangioma and a 4-month-old male baby with a mixed infantile hemangioma. Two of them also received pulsed dye laser treatment. They did not reach complete or nearly complete resolution of infantile hemangiomas at week 25. These patients experienced regrowth of their infantile hemangioma after 20 months of age and took propranolol after the age of 24 months. There were no severe adverse effects. Propranolol may not only be therapeutic but also prophylactic. Patients with infantile hemangiomas who have taken oral propranolol should be followed up at least 6 months after cessation of treatment, especially infantile hemangiomas on the cheek, and those with partial response to propranolol may require close attention in prolonged growth.

Thirty-two Japanese cases of infantile hemangiomas treated with oral propranolol.

Infantile hemangiomas undergo rapid growth during early infancy followed by gradual involution. Infantile hemangiomas sometimes impair vital functions or cause disfigurement. Thirty-two Japanese patients between the ages of 1 and 4 months with proliferating infantile hemangiomas received oral propranolol on an outpatient basis. The success rate (complete or nearly complete resolution) at week 25 was 56% (18/32). Two patients dropped out because of a personal reason and moving out. Recurrence after termination of treatment was seen in six patients. Adverse events occurred in 16 patients. There were no adverse events on day 1 (initiation of treatment at a dose of 1 mg/kg per day) and day 8 (dose increase to 2 mg/kg per day). One patient was hospitalized due to pneumonia, and suspended propranolol for 26 days. Oral propranolol at 2 mg/kg per day is effective and safe in Japanese patients with infantile hemangiomas.

Novel and recurrent ATP2A2 mutations in Japanese patients with Darier's disease.

Darier's disease (DD, keratosis follicularis: OMIM#124200) is an autosomal dominant skin disorder characterized by multiple dark brown keratotic plaques and warty papules covered by thick crusts. Most cases of DD are caused by mutations in ATP2A2, which is expressed in both the skin and the brain. ATP2A2 encodes the cardiac muscle SERCA2a protein and the ubiquitously expressed SERCA2b. SERCA2 plays an important role as a calcium pump. It is thought that a mutation in ATP2A2 causes dyskeratosis and abnormality of cell-cell adhesion. Here, we report five DD patients from five independent families who presented or were referred to the Nagoya University Hospital in the past five years. We detected five mutations in ATP2A2, including a previously unreported mutation. We observed no apparent genotype/phenotype correlation between types and sites of the ATP2A2 mutations and DD phenotypes in the present series of DD patients. Genetic diagnosis from ATP2A2 mutation search is useful for the definite diagnosis of DD, although it is difficult to predict the severity and prognosis of skin symptoms from the results of the ATP2A2 mutation analysis in DD patients.

A case of scleredema adultorum successfully treated with narrow-band ultraviolet B phototherapy.

Scleredema adultorum, also known as scleredema of Buschke, is a rare connective tissue disease with unknown etiology, which is characterized by diffuse skin induration of face, neck, upper chest, back, shoulders and arms. Although there is no established treatment for this disease, the efficacy of phototherapy has been reported. We herein describe a case of scleredema adultorum successfully treated with narrow-band ultraviolet B and discuss a potential mechanism explaining its efficacy for fibrotic skin diseases.

Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes.

BACKGROUND: CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes. OBJECTIVE: To identify the mechanism underlying CCL22 production by HaCaT cells. METHODS: We investigated the signal transduction pathways by which TNF-α and IFN-γ stimulate HaCaT cells to produce CCL22 by adding various inhibitors. RESULTS: TNF-α- and IFN-γ-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1. CONCLUSION: Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.