Case of atopic dermatitis concurrent with idiopathic thrombocytopenic purpura,whose serum thymus and activation‐regulated chemokine level remained undetectable

We report a 9‐year‐old Japanese female patient with atopic dermatitis associated with idiopathic thrombocytopenic purpura. She demonstrated high serum immunoglobulin (Ig)E and IgE specific to several environmental allergens, but extremely low serum thymus and activation‐regulated chemokine (TARC) levels regardless of the disease progression. This case suggests platelets as the main source of serum TARC.     

Serum thymus and activation‐regulated chemokine as disease activity and response biomarker in alopecia areata

Serum thymus and activation‐regulated chemokine/CCL17 (sTARC) is known as a good indicator for atopic dermatitis severity. Herein, we investigate whether sTARC correlates with severity and therapeutic response for alopecia areata (AA) in our 121 patients. The sTARC mean of AA totalis and universalis was significantly higher than mild AA. Next, we compared sTARC of diffuse AA (n = 14) and severity‐controlled patchy AA (n = 32) and found that sTARC in diffuse AA (564.2 ± 400.0 pg/mL) was significantly higher than that of the patchy type (344.0 ± 239.8 pg/mL), suggesting a potential role of TARC in active progression of diffuse AA. Ten patients with diffuse AA were treated with i.v. corticosteroid pulse therapy. Then, we tested whether sTARC can predict prognosis after the pulse therapy and found that baseline sTARC in the poor responders (1025.5 ± 484.8 pg/mL) was significantly higher than that in the good responders (complete remission at 24 months after the pulse therapy, 347.8 ± 135.7 pg/mL), indicating sTARC as a response biomarker in the corticosteroid pulse therapy for diffuse AA. Finally, to investigate TARC production in the affected hair follicles, we performed immunohistochemical double staining of TARC and CD68 using scalp skin specimens of diffuse AA with high titers of sTARC. The results showed their co‐localization in the infiltrating cells around the AA hair follicles, suggesting that TARC is mainly produced from CD68⁺ histiocytes. In conclusion, sTARC is a disease activity and response biomarker in AA, providing new insight beyond the T‐helper 1/2 paradigm to solve the immunological pathogenesis of AA.     

Elevated serum levels of soluble CD30 are associated with atopic dermatitis, but not with respiratory atopic disorders and allergic contact dermatitis

Type 2 helper T-cell immune responses can be demonstrated in the human atopic disorders atopic dermatitis and allergic asthma/rhinoconjunctivitis. The CD30 (Ki-1) antigen, originally described on Hodgkin and Reed-Sternberg cells, has recently been proposed as a marker of T cells with potent B-cell helper activity producing IL-5 and γ-IFN, as well as on CD4+ and CD8+ T cells with a Th2 cytokine profile. As a soluble form of CD30 (sCD30) is released by CD30+ cells in vivo , we studied its clinical significance in atopic disorders compared with allergic contact dermatitis and healthy controls. Elevated sCD30 levels were associated with atopic dermatitis ( P  < 0.0001), but not with respiratory atopic disorders or allergic contact dermatitis. sCD30 levels in patients with atopic dermatitis were independent of serum IgE. The particular occurrence of serum sCD30 in patients with atopic dermatitis indicates a special regulatory function of CD30+ cells in this disease.     

Distinct age‐matched serum biomarker profiles in patients with cutaneous T‐cell lymphoma

Immunological functions decline with age. Because MS/SzS predominately affects the elderly, it is important to distinguish age‐related from cancer‐specific changes. Also, MF and SzS are malignancies of CD4⁺ T‐lymphocytes, further compromising an immune state of the patients. The objectives of this study were to distinguish disease‐specific immunological deterioration by performing comparative age ‐ matched Luminex multiplex assessment of 34 serum biomarkers between patients with MF/SzS, HIV‐infected individuals and normal controls. Controlling for age, expression level appears to significantly differ between patients with MF/SzS and controls for the following biomarkers: G‐CSF, IL‐5, MIP‐1β, TNF‐α, VEGF, EOTAXIN, IL‐8, IL‐12, IL‐2R, IP10, MCP‐1, MIG, TNFR1 and TNFR2 (P < 0.05), while others showed normal age‐related changes. Interestingly, cluster analysis placed MF/SzS profiles closer to HIV. This further underscores an immunologically compromised state of patients with MF/SzS and suggests its potential self‐perpetuating role in disease progression.     

CD20‐Positive nodal natural killer/T‐cell lymphoma with cutaneous involvement

CD20‐positive natural killer (NK)/T‐cell lymphoma is extremely rare. We describe a case of a CD20‐positive nodal NK/T‐cell lymphoma with cutaneous involvement in a 32‐year‐old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA‐1 and CD20 but negative staining for other B‐cell markers, including CD79a and PAX‐5 and T‐cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein–Barr virus‐encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T‐ and B‐cells.     

Alteration of serum thymus and activation‐regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti‐interleukin‐17A agents

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side‐effects of biologics, dose‐reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation‐regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI‐clear with biologics than in the group which did not achieve PASI‐clear. Among biologics, the group treated with secukinumab, an anti‐interleukin (IL)‐17A agent, showed significantly higher TARC level compared with the group treated with anti‐tumor necrosis factor agents. In certain populations achieving PASI‐clear, serum TARC level may be a potent marker reflecting better response to IL‐17A inhibitors, and in this case step down of treatment for psoriasis is possible.     

Primary cutaneous follicular helper T‐cell lymphoma: diagnostic pitfalls of this new lymphoma subtype

The recently proposed entity of cutaneous follicular helper T (T_FH) cell lymphoma (CT_FHCL) harbors distinct clinical and histopathologic features. Here, diagnostic pitfalls are exemplified in a case report and by review of the literature. A 45‐year‐old patient developed rapidly growing nodules and plaques on upper arms and buttocks, which were initially misdiagnosed as primary cutaneous follicle center B‐cell lymphoma (CFCL). Consequently, systemic therapy with rituximab failed and consecutive skin biopsies revealed CT_FHCL (CD3+CD4+CD10+PD‐1+bcl6+ICOS+CXCL13+). Interestingly, the prima vista PD‐1‐positive and CD10‐positive tumor cells lost PD‐1 expression in follow‐up biopsies while retaining CD10, ICOS and CXCL13 expression. All biopsy specimens displayed an identical clonal T‐cell population. Initially, nodules were controlled by local radiotherapy and oral psoralen combined with ultraviolet A (PUVA) therapy. However, disease recurred and progressed rapidly with disseminated nodules. Treatment with bexarotene, methotrexate and polychemotherapy failed to stop disease progression. Finally, modified total skin electron beam radiation resulted in complete remission. Disease stabilized on maintenance therapy with bexarotene in combination with ultraviolet A (UVA) therapy. The case highlights that because of concomitant B‐cell stimulation, CT_FHCL clinicopathologically is prone to be mistaken for CFCL. Importantly, CT_FHCL might lose PD‐1 while retaining CD10 expression in later stages, which may lead to confusion in distinguishing CT_FHCL from CFCL.