Successful treatment with granulocyte and monocyte adsorption apheresis for plaque-type skin lesions in patients with psoriatic arthritis.

INTRODUCTION: Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly for refractory skin diseases, such as generalized pustular psoriasis and psoriatic arthritis (PsA). METHODS: Four patients with PsA who were refractory to previous treatments were enrolled. They received five or ten sessions of GMA. We assessed the clinical conditions of each patient and laboratory findings before and after GMA. RESULTS: GMA was effective in plaque-type skin eruptions in all four patients with PsA. It was also effective in joint symptoms in three patients with PsA with mild symptoms, but was ineffective in one patient with severe joint symptoms. CONCLUSION: GMA may be recommended to PsA patients with skin eruptions and mild joint symptoms.

Generalized Pustular Psoriasis in Pregnancy: Current and Future Treatments.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease characterized by sudden widespread eruption of sterile pustules with or without systemic symptoms. GPP may be life threatening in cases with severe complications such as cardiovascular failure, acute respiratory distress syndrome, and serious infections. Impetigo herpetiformis (IH) is a GPP that is induced and exacerbated by pregnancy and occurs most frequently during the last trimester. IH may result in poor or fatal neonatal outcomes, including placental insufficiency, fetal abnormalities, stillbirth, and early neonatal death. Most patients have prompt remission in the postpartum period; however, earlier appearance and more severe symptoms are observed during subsequent pregnancies. Appropriate treatment and close monitoring of the mother and fetus are vital for the management of patients with IH. Particular attention is required for the management of patients with IH to avoid an influence on the fetus. However, data regarding treatments for GPP in pregnant women are sparse. Over the last decade, many patients with IH have been treated with cyclosporine, corticosteroids, tumor necrosis factor-α inhibitors, interleukin (IL)-17 and IL-12/23 inhibitors, and granulocyte and monocyte adsorption apheresis (GMA). GMA may be an important option for patients with IH as it is presently one of the safest available therapeutic options, but there have been no reports to fully confirm its safety in pregnant patients with GPP. Alternatively, based on recent advances in the understanding of the role of the IL-36 axis in the pathogenesis of GPP, biologic agents that target the IL-36 pathway may demonstrate promising efficacy in IH.

Epidermal Nevus Syndrome Associated with Dwarfism and Atopic Dermatitis.

Epidermal nevus syndrome (ENS) is a congenital disorder characterized by widespread linear epidermal lesions consisting of epidermal nevus and extracutaneous involvements, especially of the central nervous system and skeletal system. Garcia-Hafner-Happle syndrome, also known as fibroblast growth factor receptor 3 (FGFR3)-ENS, is characterized by a systematized keratinocytic EN of soft and velvety type with neurological abnormalities such as seizures, intellectual impairment, and cortical atrophy. We present a case of a 9-year-old Japanese boy afflicted with Garcia-Hafner-Happle syndrome associated with dwarfism and atopic dermatitis. We show the results of physical examination, DNA analysis, and imaging studies and discuss the mutation underlying the child's disorder.

Imaging findings of trichilemmal cyst and proliferating trichilemmal tumour.

PURPOSE: The purpose of this study was to evaluate computed tomography and magnetic resonance imaging of benign trichilemmal cysts and proliferating trichilemmal tumours. METHODS: Nineteen histologically confirmed cutaneous lesions with trichilemmal keratinisation (12 trichilemmal cysts and seven proliferating trichilemmal tumours) were enrolled. Among them, 10 lesions (six trichilemmal cysts and four proliferating trichilemmal tumours) were examined by computed tomography, while 13 lesions (eight trichilemmal cysts and five proliferating trichilemmal tumours) were examined by magnetic resonance imaging. Computed tomography and magnetic resonance imaging characteristics were retrospectively reviewed. RESULTS: Sixteen lesions (84%, 10 trichilemmal cysts and six proliferating trichilemmal tumours) occurred on the scalp. Lobulated margins were observed in five lesions (26%, three trichilemmal cysts and two proliferating trichilemmal tumours). With respect to computed tomography attenuation, calcification (>200 Hounsfield units) was observed in seven lesions (70%, five trichilemmal cysts and two proliferating trichilemmal tumours), hyperdense areas (≥80 and ≤200 Hounsfield units) in six (60%, three trichilemmal cysts and three proliferating trichilemmal tumours), and soft tissue density areas (<80 Hounsfield units) in nine (90%, five trichilemmal cysts and four proliferating trichilemmal tumours). On T1-weighted images, intratumoral hyperintensity was only observed in eight trichilemmal cysts but no proliferating trichilemmal tumours (100% vs. 0%, P<0.01). On T2-weighted images, hypointense rim and intratumoral hypointensity was observed in all 13 lesions (100%, eight trichilemmal cysts and five proliferating trichilemmal tumours), and linear or reticular hypointensity was observed in 10 (77%, six trichilemmal cysts and four proliferating trichilemmal tumours). CONCLUSION: Trichilemmal cysts and proliferating trichilemmal tumours predominantly occurred on the scalp with calcification, and usually exhibited linear or reticular T2 hypointensity. Intratumoral T1 hyperintensity may be a useful imaging feature for differentiating trichilemmal cysts from proliferating trichilemmal tumours.

Magnetic Resonance Imaging Characteristics of Poroma and Porocarcinoma.

PURPOSE: The purpose of this study was to evaluate magnetic resonance (MR) imaging findings of poroma and porocarcinoma. METHODS: Six patients (3 male, 3 female; age range, 40-84 years; mean age, 61 years) with histologically confirmed skin appendage tumors with apocrine and eccrine differentiation (2 poromas and 4 porocarcinomas) were enrolled. All patients underwent preoperative MR imaging and the MR images were retrospectively reviewed. RESULTS: The configurations were classified as pedunculated solid in 5 lesions and subcutaneous cystic with mural nodules in 1. Well-demarcated deep tumor margins and smooth skin surfaces were observed in all 6 lesions, and peritumoral fat stranding was observed in 2. In all 5 pedunculated solid lesions, T2-hyperintense foci, T1 hyperintensity, and homogeneous solid components were observed within the lesions. CONCLUSIONS: Poroma and porocarcinoma usually exhibited pedunculated solid homogeneous lesion. Intratumoral T2-hyperintense foci and T1 hyperintensity were observed in pedunculated solid lesions.

Validation of measurement scores for evaluating vascular anomaly skin lesions.

Vascular anomalies comprise a heterogeneous group of disorders caused by abnormal proliferation or development of vascular and/or lymphatic vessels. Vascular anomalies present with various symptoms and complications, but no standardized methods evaluate their severity, and to measure treatment outcomes is difficult. To assess the responsiveness of measurement scores for evaluating vascular anomaly skin lesions, we conducted a validation study to compare these measurement scores with patients' objective data. In this study, data were collected from treated and untreated patients. Skin lesions were photographed at baseline and after a follow-up period of 3-6 months. The volume of skin lesions, the degree of red or purple coloration, and color tone were measured objectively. Two external dermatologists evaluated patients' photographs and determined scores, which represented criteria for improvements in skin lesions (size and color) and 6-point Physician Global Assessment scores. The correlation between these scores and patients' objective data (lesion volume and color) was assessed to validate the scores. Twenty-three cases of vascular anomaly (seven vascular tumors, five lymphatic malformations, three venous malformations, and eight lymphatic-venous malformations) were examined. Scores for improvements in vascular anomaly skin lesions (size and color) correlated with a change in lesion volume, the degree of red or purple coloration, color tone score, and 6-point Physician Global Assessment score. Our findings suggest that these measurement scores are responsive to changes in vascular anomaly skin lesions after observation.

Imaging findings of cutaneous angiosarcoma of the scalp: Comparison with cutaneous squamous cell carcinoma.

PURPOSE: This study aimed to evaluate imaging findings of cutaneous angiosarcoma (cAS) of the scalp compared with those of cutaneous squamous cell carcinoma (cSCC). METHODS: This study included 15 patients with primary cAS and 10 with primary cSCC of the scalp. Seven patients with cAS and eight with cSCC underwent magnetic resonance imaging, and 11 patients with cAS and eight with cSCC underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomography imaging. Imaging findings for both pathologies were retrospectively reviewed and compared. RESULTS: All 15 cAS cases were elevated lesions with an obtuse angle, invading the subcutaneous fat tissue. Multiple lesions were observed in only five cAS cases (33%) and no cSCC cases. Maximum diameter-to-height ratio was significantly higher in cAS than in cSCC (3.3 ± 1.0 versus 2.3 ± 0.6; p < 0.01). On T2-weighted images, intratumoral hypointensity (86% versus 13%; p < 0.01) and mixed hyper- and hypointensity (71% versus 0%; p < 0.01) were observed more frequently in cAS than in cSCC. No significant differences were observed between cAS and cSCC regarding flow void (29% versus 25%; p = 0.656). Maximum standardized uptake values were marginally significantly lower in cAS than in cSCC (5.6 ± 3.1 versus 10.5 ± 6.6; p = 0.078). CONCLUSIONS: Cases of cAS of the scalp always exhibited flat elevated lesions with invasion of the subcutaneous fat tissue. Compared with cSCC, intratumoral hypointensity and mixed hyper- and hypointensity on T2-weighted images were more frequent in cAS. These findings will help with the differential diagnosis of cAS.

MR imaging findings for differentiating cutaneous malignant melanoma from squamous cell carcinoma.

PURPOSE: This study aimed to assess the efficacy of using MR imaging findings for differentiating cutaneous malignant melanoma (cMM) from cutaneous squamous cell carcinoma (cSCC). METHODS: Preoperative MR images of patients with histopathologically proven primary cMM and primary cSCC were retrospectively reviewed and compared between the two pathologies. RESULTS: A total of 16 patients with primary cMM (7 men and 9 women; age range, 45-97 years; median age, 75 years) and 49 with primary cSCC (37 men and 12 women; age range, 46-90 years; median age, 76 years) were enrolled in this study. Intratumoral T1 hyperintensity compared to that of the dermis was more frequently observed in cMM than in cSCC (50 % vs. 4 %; p < 0.01). Superficial depression (51 % vs. 19 %; p < 0.05), superficial irregular margins (55 % vs. 25 %; p <  0.05), and reticular or linear T2 hyperintensity (27 % vs. 0 %; p <  0.05) were more frequently observed in cSCC than in cMM, respectively. CONCLUSIONS: cMM predominantly exhibited intratumoral T1 hyperintensity, whereas cSCC predominantly exhibited superficial depression, superficial irregular margins, reticular or linear T2 hyperintensity.

Indoleamine 2,3-Dioxygenase 2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme known to suppress immune responses, and several reports have showed that it is associated with psoriasis. IDO2 is an isoform of IDO1, recently identified as a catalytic enzyme in the tryptophan-kynurenine pathway, which is expressed in dendritic cells and monocytes. The expression of IDO2 in immune cells suggests that IDO2 may contribute to immune functions. However, the role of IDO2 in the pathogenesis of psoriasis remains unclear. In this study, to elucidate the role of IDO2 in psoriasis, we assessed imiquimod (IMQ)-induced psoriasis-like dermatitis in IDO2 knockout (KO) mice. Skin inflammation, evaluated by scoring erythema, scaling, and ear thickness, was significantly worse in the IDO2 KO mice than in the wild-type (WT) mice. The mRNA expression levels of TNF-α, IL-23p19, and IL-17A, key cytokines involved in the development of psoriasis, were also increased in the IDO2 KO mice. Furthermore, immunohistochemistry revealed that the number of Ki67-positive cells in the epidermis and CD4-, CD8-, and IL-17-positive lymphocytes infiltrating the dermis were significantly increased in the IDO2 KO mice. These results suggest that IDO2 might decrease IL-17 expression, thereby resulting in the suppression of skin inflammation in IMQ-induced psoriasis-like dermatitis.

A Case of Dermatomyositis Coexisting with Both Anti-Mi-2 and Anti-NXP-2 Antibodies.

Myositis-specific autoantibodies (MSAs) including anti-Mi-2 and anti-nuclear matrix protein 2 (NXP-2) antibodies have been detected in the patients with dermatomyositis (DM), and are useful tools for identifying clinical subsets of DM. MSAs are exclusively found in DM patients. Anti-Mi-2 antibody-positive DM patients show the typical skin lesions and myositis and are rarely associated with internal malignancy and interstitial lung disease (ILD). On the other hand, adult DM patients with anti-NXP-2 antibody often show calcinosis and internal malignancy, but rarely ILD. In addition, anti-NXP-2 antibody-positive DM patients have severe phenotype with myalgia, peripheral edema, and significant dysphagia, but with mild skin lesions. Herein, we report a rare case of classic DM coexisting with both anti-Mi-2 and anti-NXP-2 antibodies, clinically, without ILD or internal malignancy. Our patient had typical skin manifestations, muscle weakness, muscle pain, and general fatigue without calcinosis, peripheral edema, or dysphagia. Thus, the clinical phenotype was similar to anti-Mi-2 antibody-positive DM.

Studies of royal jelly and associated cross-reactive allergens in atopic dermatitis patients.

Royal jelly (RJ), a creamy substance secreted by honeybees, is the exclusive diet for queen bee differentiation and life maintenance. RJ has been used in cosmetics, beverages, medicines, and supplements worldwide. However, allergy is a concerning issue for RJ, especially in atopic dermatitis (AD) and asthma patients. In some cases, allergic reactions are seen after the first intake of RJ, suggesting the existence of allergens cross-reactive with RJ. Information about the cross-reactive allergens is very important for the safe application of RJ; however, study of this cross-reactivity is quite limited. In this study, we attempted to identify allergens cross-reactive with RJ by using serum samples from 30 AD patients who had never been exposed to RJ. In an enzyme-linked immunosorbent assay (ELISA) experiment, RJ-binding IgE antibodies were detected in the serum of 10 out of 30 patients, and their antibody titers ranged from 4- to 2,048-fold dilution ratios. Additionally, 3 AD patients were determined to be positive in a skin-prick test (SPT) with an RJ solution. Significant correlations were observed between the anti-RJ antibody titer and nonspecific IgE and between the anti-RJ antibody titer and the Eczema Area and Severity Index score. We further examined the cross-reactivity between RJ and 14 typical allergens by using an ELISA-inhibition assay and demonstrated that the following 6 allergens showed cross-reactivity with RJ: the European house dust mite (HDM) (Dermatophagoides pteronyssinus), American HDM (Dermatophagoides farinae), snow crab (Chionocetes spp.), edible crab (Cancer pagurus), German cockroach (Blatella germanica), and honeybee venom (Apis mellifera). In conclusion, people with a history of allergic diseases, including AD, asthma, and allergic rhinitis, should be cautioned against consuming RJ products because of the potential for cross-reactive responses to ensure the safe and successful use of RJ supplements.

Alternatively activated macrophages are associated with the α2AP production that occurs with the development of dermal fibrosis : The role of alternatively activated macrophages on the development of fibrosis.

BACKGROUND: Fibrotic diseases are characterized by tissue overgrowth, hardening, and/or scarring because of the excessive production, deposition, and contraction of the extracellular matrix (ECM). However, the detailed mechanisms underlying these disorders remain unclear. It was recently reported that α2-antiplasmin (α2AP) is elevated in fibrotic tissue and that it is associated with the development of fibrosis. In the present study, we examined the mechanism underlying the production of α2AP on the development of fibrosis. METHODS: To clarify the mechanism underlying the production of α2AP on the development of fibrosis, we focused on high-mobility group box 1 (HMGB1), which is associated with the development of fibrosis. The mouse model of bleomycin-induced fibrosis was used to evaluate the production of α2AP on the development of fibrosis. RESULTS: We found that HMGB1 induced the production of α2AP through receptor for advanced glycation end products (RAGE) in fibroblasts. Next, we showed that macrophage reduction by a macrophage-depleting agent, clodronate, attenuated the progression of fibrosis and the production of α2AP and HMGB1 in the bleomycin-induced mice. We also showed that IL-4-stimulated alternatively activated macrophages induced the production of HMGB1, that IL-4-stimulated alternatively activated macrophage conditioned media (CM) induced pro-fibrotic changes and α2AP production, and that the inhibition of HMGB1 and RAGE attenuated these effects in fibroblasts. Furthermore, the blockade of IL-4 signaling by IL-4Rα neutralizing antibodies attenuated the progression of fibrosis and the production of α2AP and HMGB1 in the bleomycin-induced mice. CONCLUSION: These findings suggest that alternatively activated macrophage-derived HMGB1 induced the production of α2AP through RAGE and that these effects are associated with the development of fibrosis. Our findings may provide a clinical strategy for managing fibrotic disorders.

Palisaded Neutrophilic and Granulomatous Dermatitis in a Patient with Granulomatosis with Polyangiitis.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) shows various clinical features and is histologically characterized by palisaded granulomas surrounding degenerated collagen. PNGD is known to be associated with a variety of systemic conditions such as rheumatoid arthritis and systemic lupus erythematosus. Furthermore, PNGD has been reported to be associated with antineutrophilic cytoplasmic antibody-associated vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis. Here, we report a case of PNGD associated with GPA, which showed the infiltration of CD163-positive M2 macrophages in the skin lesion with elevated serum level of soluble CD163 (sCD163). The serum sCD163 level was reduced to normal range after systemic steroid therapy. Thus, M2 macrophages may play a role in the pathomechanisms of PNGD associated with GPA.

Magnetic Resonance Imaging Findings Differentiating Cutaneous Basal Cell Carcinoma from Squamous Cell Carcinoma in the Head and Neck Region.

OBJECTIVE: This study aimed to evaluate the efficacy of magnetic resonance (MR) imaging in differentiating between cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC) in the head and neck region. MATERIALS AND METHODS: Among patients with cutaneous head and neck cancers, 14 with primary cBCCs and 15 with primary cSCCs with a histologic tumor height of ≥ 4 mm underwent MR examinations; the findings were then examined for correlations. RESULTS: cBCCs (71%) occurred more frequently on the nose than cSCCs (13%) (p < 0.01). The maximum diameter (23.5 ± 7.2 mm vs. 12.7 ± 4.5 mm; p < 0.01) and diameter-to-height ratio (2.8 ± 0.9 vs. 1.7 ± 0.4; p < 0.01) were significantly greater in cSCCs than in cBCCs. Superficial ulcer formation (67% vs. 21%; p < 0.05), protrusion into the subcutaneous tissue (60% vs. 21%; p < 0.05), ill-demarcated deep tumor margins (60% vs. 7%; p < 0.01), and peritumoral fat stranding (93% vs. 7%; p < 0.01) were more frequently observed in cSCCs than in cBCCs. Intratumoral T2-hyperintense foci (57% vs. 13%; p < 0.05) were more frequently observed in cBCCs than in cSCCs. CONCLUSION: cBCCs predominantly occurred on the nose with intratumoral T2-hyperintense foci, whereas cSCCs predominantly exhibited a flattened configuration, superficial ulcer formation, protrusion into the subcutaneous tissue, ill-demarcated deep tumor margin, and peritumoral fat stranding.