Ikuko Ueda-Hayakawa

Elevated serum BAFF levels in patients with sarcoidosis: association with disease activity

OBJECTIVE The purpose of this study was to determine serum levels of B-cell-activating factor (BAFF) and its clinical association in patients with sarcoidosis. METHODS; Serum levels of BAFF from 37 patients and 21 healthy subjects were examined by ELISA. Serum angiotensin-converting enzyme (ACE), lysozyme and IFN-γ levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-γ, IL-4 or IL-10 and their expression of membrane and soluble BAFF were analysed by flow cytometry or ELISA. Peripheral B cell subsets were analysed by flow cytometry. BAFF expression in the granuloma of the skin was examined by immunohistochemistry. ANAs were determined by indirect IF using HEp-2 cells as a substrate. RESULTS Serum BAFF levels were significantly elevated in sarcoidosis patients when compared with healthy controls. The frequency of skin and eye involvement was significantly higher in patients with elevated serum BAFF than in patients with normal levels. Serum BAFF levels were correlated with serum levels of ACE, lysozyme and IFN-γ. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-γ induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naïve B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity. CONCLUSION Serum BAFF levels can be used as a surrogate marker of disease activity in sarcoidosis patients. Increased BAFF may be related to the pathogenesis of sarcoidosis.

Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement

Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin‐2 receptor (sIL‐2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL‐2R compared with two other common markers, angiotensin‐converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL‐2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL‐2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL‐2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression‐specific signs by imaging analysis. Receiver–operator curve analysis showed that sIL‐2R was a better marker at the threshold cut‐off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL‐2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow‐up period. In conclusion, sIL‐2R may be considered a good marker for diagnosis and a potential indicator of disease activity.

High incidence of pulmonary arterial hypertension in systemic sclerosis patients with anti-centriole autoantibodies

Abstract Systemic sclerosis (SSc)-related autoantibodies are useful tools in identifying clinically homogenous subsets of patients and predicting their prognosis. In this report, we described five SSc patients with anti-centriole antibodies. All five patients were females and had digital ulcers/gangrene. Four of five (80%) patients had pulmonary arterial hypertension (PAH). None of the five patients had active pulmonary fibrosis or developed renal crisis. Anti-centriole antibodies may be a marker for PAH and digital ulcers/gangrene.

Early cutaneous eruptions after oral hydroxychloroquine in a lupus erythematosus patient: A case report and review of the published work

Hydroxychloroquine (HCQ) is an effective treatment of lupus erythematosus. Although adverse effects, mainly gastrointestinal and cutaneous manifestations, are rare, they may result in the cessation of medication in some patients with severe reactions. Therefore, the evaluation of a patients condition is important for a dermatologist to decide whether to cease or continue HCQ. We herein report a case of a 36‐year‐old Japanese woman with systemic lupus erythematosus and cutaneous eruptions caused by the p.o. administration of HCQ. Because she wanted to continue the medication and had only mild cutaneous eruptions without any adverse effects in other organs, we continued HCQ with careful monitoring. All cutaneous eruptions disappeared within 1 week. We also reviewed published case reports on skin lesions that developed after HCQ treatments, and propose strategies for early cutaneous eruptions after HCQ treatments. When the cutaneous reactions are mild without any reactions in other organs, withdrawal of the drug is not required. However, when cutaneous eruptions are accompanied by some common reactions, HCQ needs to be stopped for a period of time and may subsequently be carefully re‐administrated.

Annular lesions of cutaneous sarcoidosis with granulomatous vasculitis

Sarcoidosis is known to be involved in diseases with vasculitis as sarcoid vasculitis. However, vasculitis in cutaneous sarcoidal lesions is extremely rare. Here we describe a case of sarcoidosis with multiple annular skin lesions with granulomatous vasculitis. A 62‐year‐old female was diagnosed with sarcoidosis by chest‐abdominal computed tomographic examination and laboratory tests. The skin lesions had appeared on her lower limbs 2 years before. Physical examination showed multiple infiltrated annular eruptions on the lower extremities. A skin biopsy of an area of erythema showed multiple non‐caseating epithelioid cell granulomas in the dermis and subcutaneous fat and granulomatous vasculitis with fibrinoid degeneration in the subcutaneous fat. There are two types of vasculitis in sarcoidosis: leukocytoclastic and granulomatous vasculitis. Ulcers and livedo were more common in granulomatous vasculitis than in leukocytoclastic vasculitis. The present case had unique annular skin lesions of sarcoidosis with granulomatous vasculitis.

Cutaneous necrotizing vasculitis in a patient with dermatomyositis positive for anti-PL-7 antibody

ejd.2013.2163 Auteur(s) : Ikuko Ueda-Hayakawa1 uedaik@hirakata.kmu.ac.jp, Taro Kusuyama1, Taiki Isei1, Yoshio Ozaki2, Yasuhito Hamaguchi3, Manabu Fujimoto3, Kazuhiko Takehara3, Hiroyuki Okamoto1 1 Department of Dermatology, 2 Department of Rheumatology and Clinical Immunology, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka 573-1191, Japan 3 Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Autoantibodies against several aminoacyl-tRNA [...]

Four cases of anti‐Mi‐2 antibody‐positive dermatomyositis: relationship between anti‐Mi‐2 antibody titre and disease severity and activity

Editor Anti-Mi-2 antibody was found to be a specific marker for dermatomyositis (DM). Patients with anti-Mi-2 antibody generally have a more favourable prognosis, such as milder muscle involvement and a lower risk of interstitial lung disease (ILD) and malignancy. However, it currently remains unclear whether the anti-Mi-2 antibody titre correlates with disease severity and activity, or if repeated testing for disease monitoring is beneficial. Therefore, we evaluated the relationship between clinical severity or activity and anti-Mi-2 antibody levels or ANA titres of four patients with anti-Mi-2 antibody-positive DM. Case 1: A 56-year-old man noted erythema on the face 2 years ago, and skin eruptions gradually expanded to the trunk. Diffuse purplish erythema from the forehead to the cheeks, flagellate erythema on the upper back, periungual erythema, punctate haemorrhage on the perionychium and Gottron’s sign were observed. Case 2: A 62-year-old man had skin rash on his face and hands for 6 years. He was referred to our hospital due to an increase in serum CK levels. Mild oedematous erythema on both eyelids and erythema on the forehead and around the nose were observed. Periungual erythema, punctate haemorrhage and Gottron’s sign were noted. Case 3: A 36-year-old man was admitted to our hospital with a 3-year history of erythema on the face and both hands. Slight erythema around the nose and neck, periungual erythema, Gottron’s sign on both hands and punctate haemorrhage were observed. Case 4: A 69-year-old woman had erythema on her face and back and developed muscle weakness 3 years ago. Erythema around the nose, eyebrows and forehead, periungual erythema, punctate haemorrhage and Gottron’s sign were observed. We performed an immunoprecipitation (IP) assay with S-labelled K562 cell extracts as previously reported and identified the anti-Mi-2 antibody in all patients. Other circulating antibodies were not detected, except for anti-SS-A antibody in case 4. The clinical features of the four patients are summarized in Table 1. We diagnosed all four cases as DM from skin eruptions and myositis. Muscle weakness was observed in all cases, whereas none had ILD or malignancy. All patients showed Gottron’s sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema. Truncal erythema was observed in two of the four patients, but was very mild. The patients in this study showed similar clinical manifestations with characteristic DM skin lesions as previously reported. After treatment initiation with 1 mg/kg/day prednisolone, skin eruptions and muscle weakness improved in all cases. Table 2 shows serial ANA and anti-Mi-2 antibody titres in these patients. We did not measure the titre before treatment initiation in case 4; however, the other 3 cases showed a decrease in their titres with the treatment. Cases 1 and 2 had higher CK levels and more severe muscle weakness than case 3. Correlated with the disease severity, ANA titres were higher in cases 1 and 2 and anti-Mi-2 titres were higher in case 2 than in case 3. Moreover, ANA titre showed decreases during treatments in cases 1, 2

Up-regulated expression of CD86 on circulating intermediate monocytes correlated with disease severity in psoriasis

BACKGROUND The number of intermediate monocytes (CD14++CD16+) increases in many inflammatory conditions. However, it is not yet known which functional markers expressed by these populations are linked to the pathogenesis of psoriasis. OBJECTIVES We evaluated the expression of functional markers on circulating intermediate monocytes. Our goal was to correlate specific populations and their markers with the clinical severity of psoriasis. METHODS A cohort of 43 psoriatic patients was subjected to analysis. The proportion of intermediate monocytes with CD86 expression was evaluated by flow cytometry. Serum beta defensin-2 levels were measured by ELISA. Immunofluorescent staining was performed in order to identify the presence of CD14+CD16+ cells that co-expressed CD86 in affected skin tissues. RESULTS Upregulated expression of CD86 on the intermediate subset (but not the number of intermediate monocytes) correlated with clinical severity as measured by PASI scores and serum beta defensin-2 levels. Immunostaining also showed the presence of CD86+CD14+CD16+ cells in the epidermis and dermis of psoriatic plaques, which was associated with increased epidermal proliferation. CONCLUSION These results suggest that the expression of CD86 on circulating intermediate monocytes could be used as an index in clinical practice and provide novel insights into how these cells join a complex immune network under the pathological conditions of psoriasis.

Autoantibody to transcriptional intermediary factor-1β as a myositis-specific antibody: clinical correlation with clinically amyopathic dermatomyositis or dermatomyositis with mild myopathy

Myositis‐specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)‐1γ and TIF‐1α are known to be MSAs. Previously, we reported that TIF‐1β is also targeted in patients with DM with or without concomitant anti‐TIF‐1α/γ antibodies.

Case of Japanese carpenter bee (Xylocopa appendiculata circumvolans) stings

been reported in Japan from 1976 to 2016. Twelve patients had underlying disorders, which might have caused immunosuppression. Recently, cutaneous Purpureocillium infection also occurred in patients who had received lung, heart or liver transplantation as well as renal transplantation. Multiple nodules or ulcers occurred on the face, forearms and legs. The most important issue in our case was to preserve renal function of the transplanted kidney during itraconazole or voriconazole therapy. Initially, itraconazole induced the increase of the serum tacrolimus level and it was ineffective. A consensus in antifungal therapy of Purpureocillium infection has not been established. The MIC of various antifungal agents suggested that voriconazole was the best drug to inhibit the growth of isolated P. lilacinum in our case. Several articles described the efficacy of voriconazole treatment alone or in combination with terbinafine in P. lilacinum infection. Ezzendin et al. suggested the usefulness of the antifungal susceptibility testing. We emphasize that antifungal susceptibility assay is necessary in recalcitrant cases.