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Confluent and reticulated papillomatosis (CRP) is a rare skin disorder that develops in young adults and presents as persistent brown papules and plaques predominantly affecting the intertriginous areas, however, its etiopathogenesis remains elusive. Herein, we report a probable case of CRP with lesional hypohidrosis as detected by sweat test and provide insight into the pathomechanism. A 23-year-old man presented with nine-months history of painful sensation on his trunk without any skin change. The result of sweat test was compatible with acquired idiopathic generalized anhidrosis. Topical heparinoid and physical exercise improved the symptoms. However, he started to notice asymptomatic brownish reticulated macules on the trunk. Intriguingly, focal hypohidrosis, as detected by sweat test was evident on the macules. In histology, the lesional skin demonstrated hyperkeratosis, acanthosis, basal melanosis, mild papillomatosis, and obstruction of the sweat duct in the upper dermis, which were not observed in the peri-lesional skin. Accumulation of the sweat in the luminal aspect of the secretory portion and dilation of the sweat duct in the deeper dermis was detected in the lesional skin, as highlighted by anti-dermcidin staining. Aquaporin 5 expression in the secretory portion was more confined to the cell membrane in the lesional skin. Both brownish macules and lesional hypohidrosis simultaneously improved in summer and exacerbated in winter. Literature review found nine reports on recurrent CRP, and obesity was thought to be a major comorbidity in recurrent CRP cases. Obesity is often associated with sweat dysregulation. This, together with the findings in our case, implied the possible contribution of focal sweating abnormality in the pathogenesis of reticulated skin lesion in our case., (© 2022 Japanese Dermatological Association.)

Background: Acquired idiopathic generalized anhidrosis (AIGA) manifests varying degrees of syringotropic inflammation., Objective: To better understand the basis of inflammation in AIGA., Methods: Changes in the extent of cell infiltration around the sweat gland/duct and the difference in the expression level of immune privilege (IP)-related/sweat gland markers before and after thermal stimulation were assessed in AIGA. We also adopted a semi-quantitative digital image analysis of sweating as detected by the starch-iodine method. The changes in sweating before and after treatment was defined as the improvement index., Results: Nine AIGA cases were analyzed. Two cases with minimal inflammation were defined as non-inflammatory type (non-inf)AIGA, while others with evident cell infiltration were defined as inflammatory type (inf)AIGA. MHC class I was significantly upregulated with downregulation of macrophage migration inhibitory factor and alpha-melanocyte-stimulating hormone exclusively in the sweat duct of infAIGA after thermal stimulation (p < 0.05). Furthermore, the extent of inflammation and the ductal dermcidin expression prior to thermal stimulation were inversely correlated (r = - 0.807), while that and the ductal claudin-1 expression after thermal stimulation was positively correlated (r = 0.875). The improvement index positively correlated with the degree of inflammation after thermal stimulation implying possible contribution of inflammation in AIGA pathophysiology. In addition, interferon-induced protein 10 and claudin-1 expression level in the sweat duct before thermal stimulation respectively correlated with the improvement index (r = 0.750, and 0.762)., Conclusion: The pathophysiology of AIGA may be subcategorized into two groups: IP-collapse possibly play some roles in infAIGA, while ductal dysfunction may exist in non-infAIGA., Competing Interests: COI disclosure The authors have no conflict of interest to declare., (Copyright © 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Mucous membrane pemphigoid (MMP) rarely coexists with another autoimmune bullous disease (AIBD). Herein, we report an extremely rare MMP case who sequentially developed pemphigus foliaceus (PF). A 72-year-old man had been treated by azathioprine monotherapy for anti-BP180 MMP for 1.5 years. Clinical findings suggestive of PF, represented by scaly erythema and erosions, started to appear approximately 1 month after the episode of diarrhea. Serological and immunohistochemical examinations confirmed the diagnosis of PF. The mucocutaneous lesions were controlled by oral azathioprine and topical corticosteroids. To our knowledge, this is a previously unreported case of PF coexistent with MMP. A literature review of MMP cases associated with AIBD elucidated that 16 out of 18 cases simultaneously developed MMP and AIBD, while only two cases were diagnosed sequentially by the changes in clinical symptoms similar to our case. The titer of anti-desmoglein 1 antibodies lineally correlated with the changes in the severity of scaly erythema. Mild but noticeable exacerbation of mucosal erosion prior to the gradual increase in anti-BP180-NC16a antibodies was also noted. Unlike in other cases where MMP/AIBD coexisted, sequential development of autoantibodies in our case cannot be explained by the epitope-spreading theory as autoantigens are micro-anatomically isolated from one other. The preceding viral infection and/or continuous moderate inflammation due to azathioprine monotherapy for MMP might have contributed to the development of PF in our case., (© 2021 Japanese Dermatological Association.)

Background: Syringotropic cell infiltration is a histological hallmark of some autoimmune diseases. However, its underlying mechanism remains unclear., Objectives: To assess the immune privilege (IP) of the human sweat gland (SwG) in homeostasis and in syringotropic autoimmune diseases., Methods: We combined quantitative digital image microdissection with immunohistochemisty to analyze IP molecule expression in SwG of normal and diseased skin. The human skin organ culture model was used to examine the influence of proinflammatory conditions on IP in SwG., Results: In the normal subjects (n = 10), major histocompatibility complex (MHC) class І expression was significantly reduced in SwGs compared to the epidermis. In contrast, IP-guardians, macrophage migration inhibitory factor (MIF) and alpha-melanocyte stimulating hormone (α-MSH) were upregulated in SwGs. MHC class І was upregulated in whole SwGs in lupus erythematosus (LE; n = 7) and scleroderma/morphea (Scl; n = 9), whereas differential expression was noted only in the secretory portion in Sjögren's syndrome (SjS) (n = 4). MIF expression level inversely correlated with that of MHC class I in all samples tested, and downregulation of α-MSH was detected in LE SwGs alone. The severity of inflammatory changes and MIF and ⍺-MSH expression were inversely correlated in LE. CD200 expression was decreased exclusively in atrophic stage of Scl. In a human skin organ culture model, intratissue injection of interferon-gamma up-regulated MHC class I and downregulated MIF and α-MSH., Conclusions: These findings indicate that SwGs enjoy IP. Dysregulated IP molecule expression may lead to SwG IP collapse and contribute to distinct inflammatory cell distribution in syringotropic autoimmune disorders., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Subcutaneous injection of azacitidine (AZA) is an important treatment option for myelodysplastic syndrome (MDS), which improves overall survival. In hematology, the incidence of AZA-induced cutaneous adverse events (AE) has been known to be relatively high, which has not been well recognized by dermatologists. Discontinuation of AZA can result in the deterioration of MDS disease activity. Therefore, on dermatological consultation, precise evaluation of AE severity and careful consideration is required for post-AE medication management. To enhance our understanding of AZA-induced cutaneous AE, we report four cases with two representative cutaneous AE subtypes and summarize the clinicopathological phenotypes and courses of the cases in the published work. Case 1, a 71-year-old man, developed neutrophilic dermatosis involving the dermis and subcutaneous tissue. The other three cases, a 75-year-old man, a 78-year-old woman and a 68-year-old man, presented injection-site erythema associated with flare-up reaction. Discontinuation of AZA was necessary for case 1 alone. The published work review delineated three major subtypes of AZA-induced cutaneous AE: systemic cutaneous reaction, neutrophilic dermatosis type and erythematous type injection-site reaction. Histologically, the first two subtypes are mostly characterized by neutrophil infiltration, while the third subtype presents lymphocytic cell infiltration. Neither AZA discontinuation nor intensive interventions were required for the erythematous type injection-site reaction, while AZA termination or systemic treatments, represented by corticosteroid administration, were preferentially conducted for the systemic cutaneous reaction or the neutrophilic dermatosis type injection-site reaction subgroup. These observations support the necessity of subtype-dependent treatment strategies for the management of AZA-induced cutaneous AE., (© 2020 Japanese Dermatological Association.)

Panton-Valentine leukocidin (PVL) is a causative agent of lethal necrotizing pneumonia and is associated with epidemic strains of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA). PVL-producing strains have rarely been isolated in Japan. However, PVL-positive CA-MRSA has been isolated much more frequently in recent years. To investigate the relevance of pvl genes (lukS/F-PV) and clinical traits in epidemic S. aureus strains, we genotyped four PVL-positive CA-MRSA strains isolated from patients with skin and soft tissue infections and measured their susceptibility to antibiotics. Three of the isolates matched the genotype of the USA300 clone, which has predominantly been isolated in the USA. The remaining strain matched the ST217 genotype, and its spa type was identical to that of PVL-positive strains previously reported in India and China. Abscess drainage was necessary in all cases, and deep cutaneous ulcers were formed in three out of four cases regardless of the genotype. The ST217 genotype strain was resistant to clindamycin, in addition to quinolones, macrolides, and aminoglycosides. Thus, diagnostic determination of lukS/F-PV should be used as a guide for selecting the treatment regimen.

Although there is a growing acceptance that sweat could play a detrimental role in various allergic skin diseases, the possibility that sweat is also involved in maintenance of skin hydration and skin-specific immune responses has not been acknowledged. We initially describe physiological role of sweat in both maintaining skin hydration and thermoregulation. The purpose of this article is to provide the reader with objective evidence that sweating is intimately linked to vital stratum corneum barrier function and usefulness of application of moisturizers in clinical care of allergic skin diseases. This review also covers how sweating disturbance would leave the skin vulnerable to the development of various allergic skin diseases, such as atopic dermatitis. New therapeutic approaches would specifically target such sweating disturbance in these allergic skin diseases., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Granuloma faciale (GF) is a rare chronic dermatosis with still unknown etiopathology, which usually presents a solitary, asymptomatic, smooth reddish-brown to violaceous plaques or nodules on the face. Various therapeutic approaches, including topical application of corticosteroid or tacrolimus and removal with laser, cryotherapy and surgery have been attempted; however, the outcome has been inconsistent. Herein, we report a case of perinasal nodular GF who repeatedly underwent surgical excisions after the failure of laser treatment. Despite its nomenclature, GF does not manifest granulomatous tissue and the lesion is histopathologically characterized by dense dermal cell infiltration devoid of granulomatous changes and not distinguished by a clear border, which partially explains the difficulty of complete removal in our case. Review of the published work delineated that GF could be largely divided into two clinical subsets: plaque and nodular types. The plaque type GF could be responsive to topical tacrolimus, an approach preferentially adopted nowadays, while nodular type GF was often resistant to topical therapies and required surgical or laser removal. The latter subset often arose around the nose. For this location, surgical excision with sufficient removal margin is sometimes technically difficult when an aesthetically acceptable outcome is expected, explaining the basis for local recurrence. Postoperative recurrence could be observed after years of disease-free period. These observations indicated that the need for respective treatment strategies for the management of distinctive GF subsets. Of note, a multidisciplinary approach combining radical resection and additional supportive intervention with long-term follow up may be required for perinasal and nodular GF., (© 2018 Japanese Dermatological Association.)

Although atopic dry skin is believed to be caused by defects in skin genes important for maintaining skin barrier function, the role of sweat in atopic dermatitis (AD) has been apparently underestimated. Given the great capacity of sweat to maintain and increase skin hydration, defective sweating responses may be a logical place to look for changes that predispose individuals to the disease. We investigated how disease process and sweating defects progress from early asymptomatic stages to the onset of clinically apparent disease by employing the impression mould technique, which allows an accurate quantification of individual sweat gland/duct activity in relation to skin surface topography. Insensible and sensible sweating responses under baseline conditions and after thermal stimulus, respectively, were measured in various stages of AD patients and healthy controls. In controls, under baseline conditions, sweat ducts/glands at the dermal folds secreted basal levels of sweat (insensible sweating), thereby maintaining skin hydration. Not only such insensible sweating but also sensible sweating markedly decreased even in the earliest asymptomatic stage and the decrease was followed by compensatory hyperhidrosis at the ridge: leakage of sweat into the dermis could represent the initial event resulting in the decreased sweating and inflammation. The defects eventually progressed involving all of the ducts/glands to develop systemic dry skin. AD skin is characterized by varying degrees of functional impairment of sweat ducts/glands depending on the stage, and this defect would be among the reasons for the inability of AD patients to maintain skin hydration., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)