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.

Moesin and stress-induced phosphoprotein-1 are possible sero-diagnostic markers of psoriasis.

To identify diagnostic markers for psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from psoriasis vulgaris and psoriatic arthritis patients were screened by two-dimensional immunoblotting (2D-IB). Based on 2D-IB and MADLI TOF/TOF-MS analyses, eleven proteins each in psoriasis vulgaris and psoriatic arthritis were identified as autoantigens. Furthermore, serum levels of moesin, keratin 17 (K17), annexin A1 (ANXA1), and stress-induced phophoprotein-1 (STIP1), which were detected as autoantigens, were studied by dot blot analysis with psoriasis patients and healthy controls. The levels of moesin and STIP1 were significantly higher in sera from patients with psoriasis vulgaris than in the controls (moesin: P<0.05, STIP1: P<0.005). The area under the curve (AUC) for moesin and STIP1 between patients with psoraisis vulgaris and controls was 0.747 and 0.792, respectively. STIP1 and K17 levels were significantly higher in sera from patients with psoriatic arthritis than in those with psoriasis vulgaris (P<0.05 each). The AUC for STIP1 and K17 between patients with psoriatic arthritis and psoriasis vulgaris was 0.69 and 0.72, respectively. The STIP1 or moesin, CK17 serum level was not correlated with disease activity of psoriasis patients. These data suggest that STIP1 and moesin may be novel and differential sero-diagnostic markers for psoriasis vulgaris and psoriatic arthritis.

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.

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 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.

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.

Expression of bleomycin hydrolase in keratinization disorders.

A neutral cysteine protease, bleomycin hydrolase (BH), is widely expressed in mammalian tissues, with the skin seeming to contain the highest level. Our previous study revealed that BH transcription is modulated both during differentiation and by cytokines. However, BH involvement in keratinization disorder is not well known. In the present study, we performed immunohistochemical studies of BH and other serine/cysteine proteases in human normal skin and lesional skin with keratinization disorders. BH-positive cells were detected in granular layers of orthokeratotic and hyperkeratotic skin diseases, such as erythrokeratoderma and lichen planus. In parakeratotic skin diseases with porokeratosis, pityriasis rubra pilaris and psoriasis, BH staining was decreased in lesional skins compared to that in normal skin. Similar results were obtained for cysteine proteases, caspase-14 and calpain I. On the other hand, cells positive for serine proteases kallikrein 5 and 7 were increased in parakeratotic and inflammatory skin diseases, such as psoriasis. Semi-quantification analysis revealed that BH- and caspase-14-positive staining had higher intensity than those of the other proteases in normal epidermis. As BH is the major citrulline aminopeptidase in normal granular layer, the alternation would have a significant effect on terminal differentiation processes, such as aberrant processing of deiminated peptides. Therefore, BH may play an important role during the late stage of epidermal differentiation.

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.

Evaluation of nail disease in psoriatic arthritis by using a modified nail psoriasis severity score index.

BACKGROUND: The Classification of Psoriatic Arthritis Study Group published new criteria for classifying psoriatic arthritis (PsA) which included nail psoriasis. Our aim was to clarify the clinical importance of nail disease in PsA patients. METHODS: We investigated the types and severity of nail disease by using the modified nail psoriasis severity score index (mNAPSI) in 23 PsA patients and 23 patients with uncomplicated psoriasis. We analyzed the relationships of mNAPSI with nail fold psoriasis, psoriasis area and severity index score, swollen and/or tender joint counts, distal interphalangeal (DIP) joint disease, acute phase reactants and the score on the Japanese version of the standard health assessment questionnaire. RESULTS: The mNAPSI in 23 PsA patients was higher than that of controls (4.8 ± 5.3 vs. 2.3 ± 3.7, P < 0.05). The severity of fingernail disease in PsA patients was significantly associated with DIP joint disease (8.6 ± 5.9 vs. 3.1 ± 3.3, P < 0.05) and nail fold psoriasis (6.7 ± 5.2 vs. 3.5 ± 5.2, P < 0.05). There were no correlations between the mNAPSI and other systemic involvements. CONCLUSIONS: The nail involvement and prolonged nail bed psoriasis were common in PsA patients. Nail fold psoriasis and DIP joint arthritis were associated with nail involvement in PsA patients. Nail psoriasis would be related to the Koebner phenomenon and local inflammatory DIP joint arthritis in PsA patients, and we suggested that nail involvement in PsA was among the disorders indicative of distal phalanx enthesitis.