Adverse effects of methotrexate in three psoriatic arthritis patients.

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

Nestin expression is increased in the suprabasal epidermal layer in psoriasis vulgaris.

We investigated the expression of both epidermal fatty acid-binding protein (FABP5), a marker of transit amplifying cells, and nestin, a putative marker of epidermal stem cells, in psoriatic epidermis and in normal human cultured keratinocytes. In lesional psoriatic epidermis, immunostaining showed that the suprabasal layer was positive for nestin, with some cells co-expressing FABP5. Flow cytometric analysis revealed that the expression of both nestin and FABP5 were increased in keratinocytes cultured in a low concentration of calcium relative to those cultured in a high concentration of calcium. These results suggest that nestin and FABP5 are expressed in actively proliferating keratinocytes in vitro and in the suprabasal layer in lesional psoriatic epidermis, and that double-positive cells may identify transit amplifying cells in the epidermis.

A case of psoriasis vulgaris with diffuse idiopathic skeletal hyperostosis involved with ossifications of posterior and anterior longitudinal ligament.

Diffuse idiopathic skeletal hyperostosis (DISH) is difficult to distinguish from various forms of inflammatory arthritis, including psoriatic arthritis (PsA), rheumatoid arthritis, and ankylosing spondylitis. A 67-year-old Japanese male had been treated for psoriasis vulgaris for 13 years. Numbness of his right arm and lower limbs and spinal stiffening had developed 7 years prior to his initial evaluation at our facility. He noticed pain mainly while exercising. There were symmetrical marginal syndesmophytes in the spine, from the thoracic vertebrae to the upper lumbar vertebrae, on radiological examinations. We therefore suspected DISH. Furthermore, ossifications of the posterior and anterior longitudinal ligaments were noted in the cervical spine. Laboratory examinations revealed a normal peripheral white blood cell count, serum C-reactive protein, and erythrocyte sedimentation rate, and he was negative for rheumatoid factor. We detected human leukocyte antigen B39 but not B27. All distal interphalangeal joints were swollen but without pain. X-ray imaging showed narrowing of the joint space, and the consolidation of the joint was recognized, but there was no new juxta-articular bone formation. Based on clinical and radiological findings, we concluded that he had DISH and not PsA. DISH was indicated by marked radiological features of the axial skeleton, particularly the thoracic spine, but may also have involved the peripheral joints. DISH is one of the entheseal disorders, and 10% of Japanese middle-aged and elderly men have DISH. Therefore, the differentiation of DISH from PsA is necessary in psoriasis patients with spinal involvement.

A case of psoriasis verrucosa successfully treated with adalimumab.

We herein report a case of psoriasis verrucosa that was successfully treated with adalimumab. A 55-year-old Japanese male had a five-year history of psoriasis vulgaris treated with topical agents. His past history included atypical psychosis treated with lithium carbonate and obesity. Despite treatment, verrucous scales developed on erythematous plaque. After treatment with adalimumab, these improved remarkably, and the patient's Psoriasis Area and Severity Index score decreased from 16.2 to 3.7.

Hair follicle stem cell marker nestin expression in regenerating hair follicles of patients with alopecia areata.

Cells that are nestin positive and keratin 15 (K15) negative are located in the hair follicle pluripotent stem cell (hfPS) area (hfPSA). The hfPSA is located within the root of the sebaceous glands, in a region just above the hair follicle bulge area. In the current study, we investigated the expression pattern of the stem cell marker nestin in the hair follicle cycling of patients with alopecia areata. In the normal human scalp, the majority of hair follicles are in the anagen phase of development. While it is often difficult to identify nestin expression in late anagen phases, nestin-expressing cells are easily identified in proliferating cells located in the hfPSA of the growing early and middle anagen phase hair follicles. In patients exhibiting alopecia areata, the middle anagen hair follicles with growing cells were found to be nestin positive and K15 negative. In contrast, the hair follicles undergoing degradation in alopecia areata patients demonstrated lymphocytic infiltration within the nestin- and K15-negative dermal papilla cells. Both the nestin-positive hfPSA and K15-positive hair follicle bulge areas were not damaged in all phases. In addition, the regenerating early anagen hair follicles demonstrated nestin-positive and K15-negative cells within the dermal papilla and in the area surrounding the hair bulb. These results suggest that the nestin-positive cells play an important role not only in the hfPSA, but also in the dermal papilla in the regenerating hair follicle.

Tuberculous gumma associated with idiopathic thrombocytopenic purpura: report of a Japanese female patient.

Our patient was a 77-year-old Japanese woman, who was under treatment for idiopathic thrombocytopenic purpura (ITP) and chronic renal failure. She had warm nodules and cord-like induration on her left knee that appeared similar to Bazin's erythema induratum. A chest X-ray examination revealed miliary tuberculosis; after anti-mycobacterial therapy, the warm nodules and cord-like induration were transformed into a cold, non-tender abscess that drained. Histopathological findings showed caseation necrosis in the subcutaneous tissue, however, mycobacteria were directly detected by Ziehl-Neelsen staining from cutaneous lesions, and cultures from the same lesion also grew Mycobacterium tuberculosis. Tuberculous gumma demonstrated multiple, cold, painless abscesses and thrombosis were also seen. This is a rare and unusual clinical form of cutaneous tuberculosis, and the result of hematogenous dissemination from a primary focus during periods of lowered resistance.

Japanese version of the early psoriatic arthritis screening questionnaire (EARP).

The early psoriatic arthritis screening questionnaire (EARP) is a simple and fast method for the identification of arthritis in patients with psoriasis. We established the Japanese version of the EARP (J-EARP) questionnaire, which includes 10 items with two choices for each. This study aimed to evaluate the utility of the J-EARP questionnaire. A total of 90 psoriasis patients, 19 psoriatic arthritis (PsA) patients and 71 psoriasis patients without joint involvement, were administered the J-EARP questionnaire. The diagnostic accuracy of the J-EARP questionnaire for the diagnosis of PsA and early-stage PsA was compared by receiver-operator curve (ROC) analysis. The J-EARP questionnaire showed similar ROC characteristics to those of the original version of the EARP (specificity 97.2% and 91.6% and sensitivity 97.2% and 85.2%, respectively) in PsA patients using the cut-off value of 3 for the J-EARP questionnaire, which was the same as that used for the original EARP questionnaire. The scores of the J-EARP questionnaire in early-stage PsA patients (<1 year from onset) were significantly higher than in those of psoriasis patients, but not lower than in those of later stage (≥1 year from onset) PsA patients. The J-EARP questionnaire is simple and fast to administer and has been proven to be robust for the identification of PsA. The J-EARP questionnaire is a useful diagnostic tool for early-stage PsA patients.

Non-pigmented fixed drug eruption induced by eprazinone hydrochloride.

A 68-year-old woman developed an upper respiratory tract infection in November 2002 and was treated with eprazinone hydrochloride, serrapeptase, carbocysteine and clarithromycin. Three days after the start of treatment, the patient noted erythema on her axilla, buttock and inguinal regions. The erythema subsided in 7 days although slight pigmentation remained. However, 7 days later the pigmentation completely disappeared. Oral eprazinone hydrochloride was given as a challenge, and 1 day later the erythema re-appeared in the same areas as on initial presentation (axilla, buttock, and inguinal regions). A fixed erythema without lasting pigmentation is attributed to eprazinone hydrochloride. Therefore, the patient was diagnosed as having a nonpigmented fixed drug eruption associated with eprazinone hydrochloride.

Microscopic polyangiitis presenting urticarial erythema and Henoch-Schonlein purpura: two case reports.

Microscopic polyangiitis (MPA) is well known as a life-threatening member of a group of systemic vasculitis diseases. We report two cases of MPA. Case 1 was a 79-year-old-man who had been diagnosed with anti-neutrophil-cytoplasmic-antibody associated vasculitis (ANCA associated vasculitis) with alveolar hemorrhage and crescentric glomerulonephritis (CrGN). He presented with urticarial erythema in the abdomen, legs and back. The skin biopsy specimens showed leukocytoclastic vasculitis on the upper dermis. Case 2 was a 74-year-old-man, who presented with purpura on the abdomen, buttocks and legs that were similar to Henoch-Schonlein purpura (HSP). He also suffered from interstinal pneumonia. His renal biopsy specimens showed glomerulosclerosis and the peripheral pattern anti-neutrophil cytoplasmic antibody (P-ANCA) was positive. We reviewed the skin eruptions that had been reported with MPA, including our cases.

[Analysis of facial lesions on adult type atopic dermatitis with anti-fungus drug (terbinafine hydrochloride) -- analysis of serum anti-Malassezia IgE antibody titers and histamine release test].

Malassezia furfur has been described as an aggravating factor in facial lesions of atopic dermatitis, and oral antifungal agents have been reported to be effective against these lesions. We used terbinafine hydrochloride to treat 15 patients with adult-type atopic dermatitis and evaluated its efficacy by measuring the improvement in facial skin manifestations, serum IgE values, and serum anti-Malassezia IgE antibody titers. A histamine release test (HRT) for Malassezia. was also performed in 6 of the 15 patients. The facial skin manifestations improved in 8 (53.3%) of the 15 patients, and there were significant simultaneous decreases in their serum IgE values. The serum anti-Malassezia IgE antibody titer decreased significantly in all 15 patients. However, no significant correlation was observed between the HRT and the facial skin manifestations. We concluded that oral terbinafine hydrochloride is effective against the facial lesions of atopic dermatitis patients and this is possibly caused by decrease of Malassezia antigen in the facial lesions.

A case of nonepisodic angioedema with eosinophilia associated with livedo reticularis and erythema before onset of edema of the legs.

The cause of angioedema with eosinophilia (AE) is unknown. Patients with AE sometimes develop pruritic eruptions or urticaria before the onset of edema. We report a case of a 37-year-old woman with nonepisodic AE who presented with erythema and livedo reticularis before the onset of edema. The patient noticed erythema on both heels as well as livedo reticularis on her right great toe 1 month prior to presentation. A biopsy specimen from the heel revealed numerous eosinophils with degranulation infiltrating the subcutaneous tissue. One month later, she developed edema on the legs. Histopathologic findings of biopsy specimens obtained from the legs revealed edema and eosinophils in the subcutaneous tissue. Some patients with AE present with pruritic eruptions prior to the onset of edema. The diagnosis of AE in our patient with leg edema of unknown cause was considered prior to the appearance of any pruritic eruptions.