Increased plasma lipocalin-2 levels correlate with disease severity and may be a marker of acute inflammatory response in patients with psoriasis.

More than a skin disease, psoriasis is also considered a systemic disorder. Lipocalin-2, an adipokine, may be a link between psoriasis and systemic inflammation. We conducted this study to measure the plasma level of lipocalin-2 and investigate its relationship with the clinical manifestations in patients with psoriasis. We assessed 62 patients with psoriasis and 31 healthy controls. Their demographic information and clinical characteristics were determined by physical examination and review of the recorded medical history. Plasma lipocalin-2 levels were measured using an enzyme-linked immunosorbent assay. Plasma lipocalin-2 concentration was significantly higher in patients with psoriasis than in the control group (P<0.001). Patients with acute psoriatic subgroups, including psoriatic erythroderma and pustular psoriasis, had significantly higher plasma lipocalin-2 levels than those with the chronic plaque type. In addition, plasma lipocalin-2 concentration positively correlates with the disease severity index, including the psoriasis area severity index, body surface area, high-sensitivity C-reactive protein, nail psoriasis severity index, and pustular severity index. In patients with psoriasis, increased plasma lipocalin-2 levels correlated with severity and indicated an active disease state. These findings suggest that lipocalin-2 may play an important role in determining the pathogenesis of acute psoriasis and may serve as a valuable clinical biomarker of this disease.

Serum Zinc Level in Patients with Severe Genital Warts: A Case-Control Study in a Dermatology Hospital.

Background: Genital warts are a common sexually transmitted disease (STD), and there is no method that completely prevents its recurrence. Recently, zinc has been used in the treatment of cutaneous warts. Nondestructive action, ease of use, and promising results with low chances of relapse were reflected in the treatment. These effects may arise from the immunomodulatory activity of zinc in the event of a viral infection. Objectives: This study was aimed at identifying the relationship between the serum zinc level and the clinical characteristics of patients with genital warts. Materials and Methods: A case-control study was conducted. Genital warts were diagnosed by clinical examination, and disease severity was demonstrated based on the number of affected sites or the spread of lesions. The serum zinc level was measured using atomic absorption spectrophotometry. Results: A total of 78 patients with genital warts and 78 healthy volunteers were enrolled in the study. The mean serum zinc level in the genital wart group was lower than that in the control group (81.83 ± 13.99 µg/dL vs. 86.66 ± 17.58 µg/dL); however, this difference was not statistically significant (P > 0.05). The mean concentrations of serum zinc in patients having more than one affected site, spread > 2 cm2, or ten or more lesions were significantly lower than those of the control group (P < 0.05). Conclusions: The results suggested that severe genital warts may be associated with a low serum zinc level in patients.

Increased serum interleukin- 17A levels correlate with disease severity and poor prognostic factors in patients with alopecia areata.

Alopecia areata (AA) is a tissue-specific autoimmune disease characterized by non-scarring and rapid onset of hair loss. Interleukin (IL)-17A is mainly produced by T helper 17 (Th17) cells and may play a crucial role in the pathogenesis of various autoimmune diseases including AA. We conducted this research to measure serum level of IL-17A in patients with AA and investigated its relationship with the clinical manifestations in patients with AA. We assessed 36 patients with AA and 20 healthy control subjects. Demographic information and clinical characteristics were determined by physical examination and via the review of medical history. Serum IL-17A was measured by using enzyme-linked immunosorbent assay. Serum IL-17A concentration was significantly higher in patients with AA than in the control group (P=0.004). The AA patients with severe presentation, personal atopy, nail abnormalities, or active phase had significantly higher serum IL- 17A levels compared to others without these signs. Increased serum IL-17A levels in patients with AA correlate with severity and indicate an active disease state. These findings suggest that IL-17A may play an important role in determining the pathogenesis of AA and may serve as a valuable clinical biomarker of this disease.

Clinical and laboratory parameters predicting cancer in dermatomyositis patients with anti-TIF1γ antibodies.

BACKGROUND: Dermatomyositis (DM) is a chronic acquired autoimmune disorder strongly associated with cancer development. Until now, identifying predictive markers indicating a high risk of cancer has challenged clinicians. Although anti-TIF1γ antibody is a major serological indicator for cancer-associated DM, many anti-TIF1γ antibody-positive DM patients lack malignancy. OBJECTIVES: To determine clinical and laboratory parameters that support cancer prediction in anti-TIF1γ antibody-positive DM patients. METHODS: Clinical and laboratory data were collected from cancer-associated and unassociated DM patients with anti-TIF1γ antibodies. Serum cytokine concentrations were measured with a cytokine array assay. The values of inflammatory cytokines in cancer prognosis were determined with a receiver operating characteristic curve analysis. RESULTS: The cancer group had a significantly higher frequency of males, older mean age and higher anti-TIF1γ antibody levels. Some inflammatory cytokines, particularly tumour necrosis factor (TNF) and TNF receptor superfamilies, had increased levels in sera that were correlated with myositis markers, cutaneous severity and DM disease activity. Moreover, these cytokines had an area under the curve (AUC) ≥0.8 and high sensitivity and specificity at their specific cut-off, even higher than anti-TIF1γ levels in cancer prediction in our DM patients. CONCLUSIONS: Our results suggest a close pathophysiological relationship among myositis, cancer and skin involvements in DM patients with anti-TIF1γ antibodies and the potential clinical significance of anti-TIF1γ antibody levels in evaluating disease severity and prognosis in DM patients. Some inflammatory cytokines, particularly TNF and TNF receptor superfamilies including BAFF, sTNF-R1 and sTNF-R2, may support cancer prediction in DM patients with anti-TIF1γ antibodies.

Imbalance toward TFH 1 cells playing a role in aberrant B cell differentiation in systemic sclerosis.

OBJECTIVE: SSc is a connective tissue disease with multisystem disorder induced by the inflammation and fibrosis following T and B cell abnormalities. Follicular helper CD4+ T (TFH) cells play a crucial role in the formation of germinal centres and specialize in interacting to aid B cell differentiation. We aimed to investigate TFH cells and their subsets to evaluate their involvement with B cell alteration in SSc. METHOD: Circulating TFH cells (cTFH), B cells and their subsets were assessed by flow cytometry. The concentration of serum cytokines was measured by cytokine array assay. Immunohistochemistry and IF were performed to evaluate the migration of TFH cells in SSc skin lesions. RESULTS: The proportion of cTFH cells did not differ from controls, but their subsets were imbalanced in SSc patients. The frequency of TFH 1 was increased and correlated with ACA titre, serum IgM or CRP levels of patients, and cytokine concentrations of IL-21 and IL-6 that induce B cell differentiation in SSc. cTFH cells from SSc showed activated phenotype with expressing higher cytokine levels compared with controls. The frequency of TFH 17 was also increased, but was not correlated with a high level of Th17 cytokines in patients' sera. Furthermore, infiltration of TFH cells was found in skin lesion of SSc patients. CONCLUSION: We here describe an imbalance of cTFH toward TFH 1 that may induce B cell alteration through IL-21 and IL-6 pathways and promote inflammation, contributing to the pathogenesis of SSc disease.

Exploring the imbalance of circulating follicular helper CD4+ T cells in sarcoidosis patients.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease characterized by the combination of Th1 and Th17 responses. Recently, several arguments have suggested a potential involvement of B cells as well as T cells in the pathogenesis of sarcoidosis. Follicular helper CD4+ T (TFH) cells are specialized in interacting with and helping B cells, and play a crucial role in the formation of germinal centers. OBJECTIVE: We sought to explore the status of TFH cells and investigate their possible pathogenic role in sarcoidosis. METHODS: TFH cells and B cells in peripheral blood were examined by flow cytometry, and serum samples were studied by cytokine arrays. Immunohistochemistry was performed to check for the presence of TFH cells in sarcoidosis skin lesions. Gene expression in isolated TFH cells was analyzed by quantitative RT-PCR. RESULTS: The proportion of circulating TFH cells was decreased. CD4+CXCR5+ TFH cells were observed in cutaneous lesions in sarcoidosis. Gene expression in circulating TFH cells and serum cytokine concentrations related to Th17 were increased in sarcoidosis patients. Gene expressions of B cell differentiation cytokines in TFH cells were not altered in sarcoidosis patients. CONCLUSION: We herein describe a decrease of circulating TFH cells and their migration to affected tissues. Circulating TFH cells are one of the potential cell types capable of producing IL-17 and enhancing Th17 responses, and may promote the chronic inflammation. We could not demonstrate a direct linkage between the imbalance of TFH cells and abnormal B cell differentiation in sarcoidosis.

Clinical characteristics of sarcoidosis patients with systemic sclerosis-specific autoantibody: Possible involvement of thymus and activation-regulated chemokine and a review of the published works.

Sarcoidosis and systemic sclerosis (SSc) are both multisystem disorders of unknown etiology. Some cases having both sarcoidosis and SSc have been reported previously. The present study was to investigate clinical features in sarcoidosis patients who possessed SSc-specific autoantibody. The pathophysiology of each disease, including shared pathways leading to the development of both conditions, is reviewed in addition to previous reports of patients with concomitant SSc and sarcoidosis. SSc-specific autoantibodies including anticentromere antibody (ACA), anti-topoisomerase I antibody, anti-RNA polymerase III antibody and anti-U1RNP antibody were examined in sarcoidosis patients. Complete medical histories, clinical examinations and laboratory tests were conducted for all patients. For reviewing previously published reports, all cases were retrieved through a PubMed search. ACA was most frequently observed in sarcoidosis patients. Plaques and papules were the most frequent as the cutaneous sarcoidosis lesions. Soluble interleukin-2 receptor was elevated in most of the cases (6/8, 75%), and thymus and activation-regulated chemokine (TARC) was elevated in all cases (6/6, 100%). Together with our two cases (cases 1 and 3), a review of previously reported cases of sarcoidosis patients concomitant with SSc showed high frequency of ACA and plaques as cutaneous lesions. We suppose that TARC may play some roles in the production of SSc-specific autoantibodies and development of concomitance with SSc in sarcoidosis, although the mechanisms remain unknown.

TARC expression in the circulation and cutaneous granulomas correlates with disease severity and indicates Th2-mediated progression in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic disorder characterized by the accumulation of lymphocytes and monocyte/macrophage lineage cells that results in the formation of non-caseating granulomas. Thymus- and activation-regulated chemokine (TARC)/CCL17 is an important chemokine in the amplification of Th2 responses, which are achieved by recruiting CCR4-expressing CD4+ T lymphocytes. TARC concentrations are known to increase in the serum of sarcoidosis patients; however, its role in the assessment of severity and prognosis of sarcoidosis remains unknown. The objective of this study is to elucidate the role of TARC in sarcoidosis by investigating its expression in peripheral blood and at inflammatory sites. We also examined its relationship with clinical features. METHODS: Serum levels of TARC, soluble interleukin 2 receptor, angiotensin-converting enzyme, and lysozyme were measured in 82 sarcoidosis patients. The Th1 and Th2 balance in circulating CD4+ T cells was evaluated by flow cytometry. The immunohistochemical staining of TARC and CCR4 was performed in order to identify the source of TARC in affected skin tissues. RESULTS: TARC serum levels were elevated in 78% of patients and correlated with disease severity. The percentage of CCR4+ cells and the CCR4+/CXCR3+ cell ratios were significantly higher in sarcoidosis patients than in normal subjects (P = 0.002 and P = 0.015, respectively). Moreover, TARC was expressed by monocyte/macrophage lineage cells within granulomas. The abundancy as well as distribution of TARC staining correlated with its serum levels. CONCLUSIONS: The present results suggest that elevations in TARC drive an imbalanced Th2- weighted immune reaction and might facilitate prolonged inflammatory reactions in sarcoidosis.

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.

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 patient's 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.