ABSTRACT
Deep-seated dermatomycosis is a rare disease that is often caused by trauma and/or systemic immunodeficiency. We describe a case of chromoblastomycosis complicated by hyalohyphomycosis that occurred simultaneously at different sites. A 92-year-old Japanese man who had been taking oral prednisolone for an IgG4-related respiratory disease visited our clinic. He developed brownish plaques with grayish-white scales with pseudo-carcinomatous hyperplasia and numerous brownish muriform cells developing in the dermis of his right hand, and multiple painful abscesses with pustules and papules and numerous hyphae within and around the histiocytes in the dermis of his right lower leg. Upon skin tissue culture and DNA sequencing, Exophiala xenobiotica and Scedosporium apiospermum were detected separately. He had severe cellular immunodeficiency indicated by low levels in the phytohemagglutinin (PHA)-stimulated lymphocyte transformation test (LTT) and serum interferon-gamma (IFN-γ), although his humoral immunity was normal. The patient died of bacterial pneumonia, despite antifungal drug treatment for 2 months. IFN-γ producing type 1 T helper (Th1) cells play an important role in the defense against fungal infections, however, corticosteroids specifically suppress Th1 cell responses and promote the induction of fungal infection. Measurement of PHA-stimulated LTT and serum IFN-γ may be useful in determining the severity and prognosis of deep-seated dermatomycosis in patients undergoing corticosteroid treatment.
ABSTRACT
BACKGROUND: Herpes zoster (HZ) rarely results in later death, but predictive biomarkers for mortality necessitates further elucidation. OBJECTIVE: To investigate immune dynamics prior to HZ event, risk factors for HZ onset, and immune status at initial HZ. METHODS: This retrospective study extracted the absolute neutrophil and lymphocyte counts (ANC and ALC, respectively) at the initial HZ date and up to 30â days before HZ. A follow-up survey was completed within 180â days of the onset of illness. RESULTS: Patients with HZ showed higher neutrophil-to-lymphocyte ratio (NLR) and lower ALC than the control at the initial date and had poorer prognosis. In the pre-onset examination, the maximum and minimum ALC values were significantly lower in patients with HZ than in the control, and the maximum ALC value in patients with HZ was lower than the minimum value in the control. The lowest ALC value was observed 7â days before the onset of HZ. An NLR value of 4.53 or more and ALC value of 0.64 × 109 cells/L or less were predictive markers of HZ development within 30â days. Patients who died after HZ had lower minimum ALC than those who survived longer. LIMITATIONS: The study had small population size, varying age distribution, and retrospective nature. The pre-onset data might have been exaggerated. CONCLUSION: HZ develops in a state of immune reconstitution with immunocompromised conditions, as part of the unmasking immune reconstitution inflammatory syndrome (IRIS). Lymphopenia prior to HZ onset is one of the most crucial factors in its pathogenesis and vital prognosis.
ABSTRACT
Although subtle barrier defects may facilitate allergen penetration, thereby enabling allergic sensitization, the relationship between sweating disturbance and skin barrier function is unknown. However, many studies on contact hypersensitivity in mice examined ear skin, which does not sweat, instead of the footpad, where sweating is uniquely present. In this study, we assessed whether sweat suppression in the footpad before hapten application provoked a skin barrier abnormality and reduced inflammatory thresholds to topical haptens. Mice without any genetic skin barrier dysfunction displayed markedly reduced inflammatory thresholds to haptens under transient sweat suppression before hapten application. Epicutaneously applied haptens penetrated the skin more robustly in the presence of sweat suppression compared with that in its absence, although this increase was abolished by exposure to high-humidity conditions. These mice displayed a subtle atopic dermatitis-like inflammation mediated by type 2 response-dominant inflammation and increased IgE responses, mimicking some events occurring in nonlesional atopic dermatitis skin in humans and in murine models. These lesions were dramatically attenuated by exposure to high-humidity conditions. In our model, hapten sensitization does not require mechanical injury, explaining why sensitization occurs through nonlesional atopic dermatitis skin. Awareness of the importance of preserving sweating responses is essential to prevent occupational contact dermatitis and atopic dermatitis.
ABSTRACT
ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes: canonical BAF (cBAF), polybromo BAF (PBAF), and a newly described non-canonical BAF (ncBAF). While cBAF and PBAF regulate fates of multiple cell types, roles for ncBAF in hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery of disrupted expression of BRD9, an essential component of ncBAF, in multiple cancers, including clonal hematopoietic disorders, we evaluate here the role of BRD9 in normal and malignant HSCs. BRD9 loss enhances chromatin accessibility, promoting myeloid lineage skewing while impairing B cell development. BRD9 significantly colocalizes with CTCF, whose chromatin recruitment is augmented by BRD9 loss, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. These data uncover ncBAF as critical for cell fate specification in HSCs via three-dimensional regulation of gene expression and illuminate roles for ncBAF in normal and malignant hematopoiesis.
Subject(s)
Chromatin , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Chromatin Assembly and Disassembly , Cell Differentiation , Hematopoietic Stem Cells/metabolismABSTRACT
The process of RNA splicing plays a pivotal role in gene expression and genetic information modification by converting pre-mRNA into mature mRNA. Dysregulation of this process has been associated with aberrant gene expression and function, leading to hematopoietic malignancies. Through recent clinical and mouse model analyses, insights have been gained into the mechanisms underlying splicing factor mutations that aid in myelodysplastic syndrome and acute myeloid leukemia. These mutations affect genes that modulate diverse cellular processes, including chromatin regulation, transcription factors, proliferation signaling, and inflammation pathway. The relationship between aberrant splicing and cancer remains unclear despite progress in understanding the functional consequences of splicing factor mutations. This review focuses on the mechanisms of disease development because of splicing factor mutations and their potential mechanism-based therapeutic applications.
Subject(s)
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Animals , Mice , RNA Splicing/genetics , RNA Splicing Factors/genetics , Hematologic Neoplasms/genetics , Myelodysplastic Syndromes/therapy , Leukemia, Myeloid, Acute/genetics , MutationABSTRACT
INTRODUCTION: Severe dermal pain triggered by sweating stimuli, such as bathing, exercise, and mental stress, significantly affects patients' daily lives. The pathomechanism underlying the sweating-induced dermal pain remains poorly understood and there exists no standard treatment for such pain. This study aims to evaluate the effectiveness of icatibant as an analgesic, a bradykinin B2 receptor antagonist, in treating sweating-induced dermal pain, and to establish the role of bradykinin in pain induction. METHODS/DESIGN: A multicenter, exploratory, crossover, single-blinded, placebo-controlled randomized, comparative study will be conducted to evaluate the efficacy of subcutaneous icatibant injection (30 mg) in treating sweating-induced dermal pain. Ten patients will be enrolled and assigned randomly in a 1:1 ratio to either the icatibant-placebo or placebo-icatibant groups. The primary endpoint is the change in the visual analog scale scores for dermal pain induced by thermal load before and after treatment with icatibant or placebo. Secondary endpoints include changes in the duration of dermal pain, blood and plasma histamine levels, serum angiotensin-converting enzyme levels, and histological evaluation of skin tissue samples at the site of dermal pain. DISCUSSION: The effectiveness of icatibant against sweating-induced dermal pain would provide clear evidence for the involvement of the bradykinin-bradykinin B2 receptor pathway in the pathogenesis of this condition. This finding may contribute to a better understanding of the underlying mechanisms of dermal pain associated with sweating stimuli and has the potential to improve patients' quality of life by suggesting potential treatment options, specifically, using drugs that inhibit bradykinin or suppress its production.
Subject(s)
Bradykinin , Quality of Life , Humans , Bradykinin/therapeutic use , Cross-Over Studies , Single-Blind Method , Sweating , Pain/drug therapyABSTRACT
We report a case of an eight-year-old boy with mucopolysaccharidosis (MPS) II with atypical skin lesions of hyperpigmented streaks along Blaschko's lines. This case presented with mild symptoms of MPS such as hepatosplenomegaly, joint stiffness, and quite mild bone deformity, which was the reason for the delay in diagnosis until the age of seven years. However, he showed an intellectual disability that did not meet the diagnostic criteria for an attenuated form of MPS II. Iduronate 2-sulfatase activity was reduced. Clinical exome sequencing of DNA from peripheral blood revealed a novel pathogenic missense variant (NM_000202.8(IDS_v001):c.703C>A, p.(Pro235Thr)) in the IDS gene, which was confirmed in the mother with a heterozygous state. His brownish skin lesions differed from the Mongolian blue spots or "pebbling" of the skin that are observed in MPS II.
Subject(s)
Iduronate Sulfatase , Mucopolysaccharidosis II , Male , Humans , Child , Mucopolysaccharidosis II/diagnosis , Mucopolysaccharidosis II/genetics , Iduronate Sulfatase/genetics , Skin , Mutation, Missense , SplenomegalyABSTRACT
BACKGROUND: In Japan, intravenous immunoglobulin (IVIG) has been approved for corticosteroid-unresponsive bullous pemphigoid (BP); however, its usage, efficacy, and safety in clinical settings remain unclear. OBJECTIVE: To elucidate IVIG efficacy, we examined the improvement in disease severity based on the Bullous Pemphigoid Disease Area Index (BPDAI). METHODS: In this 3-year (April 2016-March 2019), prospective, post-marketing, observational surveillance study, we enrolled 379 patients (51.3 % men; mean age, 74.5 years) with corticosteroid-unresponsive BP treated with IVIG from 143 institutions in Japan (720 treatment cycles). The percentage of patients who improved by at least one severity stage or whose symptoms completely resolved based on the BPDAI score was evaluated at 15, 30, and 60-90 days. RESULTS: The improvement rates at 15, 30, and 60-90 days after initial treatment in the 328 IVIG-naïve patients were 70.7 %, 83.5 %, and 84.3 %, respectively. The BPDAI score decreased rapidly and significantly by 15 days compared with that observed during pre-treatment. Further improvement was observed at 30 and 60-90 days. The corticosteroid dose and anti-BP180 antibody titers decreased significantly post-treatment (both, p < .001). Approximately 25 % of IVIG-naïve patients underwent multiple treatment cycles. The improvement rate at 30 days after the final dose was 88 %, and the symptoms completely resolved in 44 % of patients. The incidence of adverse drug reactions per cycle was 8.34 %; the most common reaction was transient thrombocytopenia. CONCLUSION: Most patients showed improvement in severity and decrease in corticosteroid dose and anti-BP180 antibody levels post-treatment, indicating that IVIG is useful for corticosteroid-unresponsive BP treatment.
Subject(s)
Pemphigoid, Bullous , Male , Humans , Aged , Female , Immunoglobulins, Intravenous/therapeutic use , Prospective Studies , Japan , Autoantibodies , Adrenal Cortex Hormones/therapeutic use , Product Surveillance, Postmarketing , AutoantigensABSTRACT
Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease in patients with SLE. BSLE is a heterogenous disease caused by autoantibodies to the basement membrane, mainly type VII collagen. The pathogenesis of the development of autoantibodies in BSLE remains unknown. We report a case of SLE taking dipeptidyl peptidase 4 inhibitors (DPP4i) who developed tense blister lesions after administration of SARS-CoV-2 vaccine. Initial erythematous lesion before administration of SARS-CoV-2 vaccine had not shown IgG deposition at basement membrane both direct and indirect immunofluorescence (IIF). However, the result of those examinations became positive after the administration of SARS-CoV-2 vaccine. Furthermore, IIF test results using NaCl split skin had shown positive against epidermal side. These observations suggest that SARS-CoV-2 vaccination triggered production of autoantibodies that cause bullous SLE. The present case fulfills the diagnostic criteria for both BSLE and DPP4i-associated bullous pemphigoid. Skin lesions were cleared after withdrawal of DPP4i. Therefore, physicians should ask patients who develop blisters after the vaccination whether they are taking DPP4i.
Subject(s)
COVID-19 Vaccines , COVID-19 , Dipeptidyl-Peptidase IV Inhibitors , Lupus Erythematosus, Cutaneous , Lupus Erythematosus, Systemic , Pemphigoid, Bullous , Humans , Autoantibodies , Blister/pathology , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/complications , COVID-19 Vaccines/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Pemphigoid, Bullous/chemically induced , Pemphigoid, Bullous/diagnosis , Pemphigoid, Bullous/complications , SARS-CoV-2Subject(s)
Herpes Zoster , Neutrophils , Humans , Retrospective Studies , Herpes Zoster/complications , Risk Factors , Herpesvirus 3, Human , Biomarkers , Lymphocytes , IncidenceABSTRACT
BACKGROUND: Given that ocular glands become infected secondarily to herpes simplex virus 1 (HSV-1) keratitis, resulting in the loss of tear production, sweat glands may also be susceptible to HSV-1 infection, resulting in sweating disturbance, which is observed frequently in atopic dermatitis. However, due to the lack of sweat glands on the hairy skin of mice, the role of sweating in the maintenance of skin hydration has not been elucidated. OBJECTIVE: To determine the relationship between HSV-1 infection of sweat glands and sweating disturbance-induced dry skin. METHODS: By using the impression mold technique, we examined the sweating response together with the detection of HSV-1 DNA in the sweat glands of footpads, the only area with sweat glands in mice, after local cutaneous HSV-1 inoculation of immunocompetent mice. RESULTS: The sweating response and skin surface hydration were significantly decreased at 7-14 days post-infection. Sweating disturbance and dry skin was markedly enhanced when HSV-1 inoculation was followed by hyperthermic stress. Both resolved spontaneously and became resistant to a second HSV-1 inoculation, associated with increased anti-HSV-IgG antibodies. HSV-1 DNA was detected in sweat glands and dorsal root ganglia. The sweating response remained decreased after subcutaneous injection with pilocarpine, correlating histologically with marked dilatation of sweat gland lumens. These findings indicate that sweating disturbance is unlikely to be the outcome of nerve damage by HSV-1 infection. CONCLUSION: Sweating disturbance could be due to HSV-induced dysfunction of sweat glands. We developed a sweating disturbance-induced dry skin mouse model by infection with HSV-1.
Subject(s)
Herpes Simplex , Herpesvirus 1, Human , Animals , DNA , Immunoglobulin G , Mice , Pilocarpine , Sweat Glands , SweatingABSTRACT
A long-standing paradox in dermatology is why skin dehydration in the fingers can be triggered by repeated water exposure despite the action of water to hydrate skin tissue. Potential clues might be provided by identifying a mechanism through which water is held in the skin of the fingers. We speculated that this mechanism would be impaired after repeated water exposure. Here, we investigated whether there might be glabrous skin-specific water-holding machinery and whether this machinery might be impaired in dry skin/hand eczema. We examined this by using an impression-mould technique, allowing for an accurate quantification of sweat gland/duct activity and optical coherence tomography. Unlike in hairy skin, sweat pores were rarely detected at the folds of the finger at baseline. Surprisingly, after water exposure, sweat pores at the folds opened and those at the ridges closed in healthy controls (HCs). Sweating in the dermal folds of the hands correlated with skin hydration, and decreased in dry skin/hand eczema, suggesting that its impairment may be one of the causes of dry skin. After repeated water exposure, basal sweating response at the folds was exhausted in patients with dry skin/hand eczema as well as HCs. This exhaustion was rescued by exposing individuals to high humidity. Basal sweating defects would be a target for dry skin/hand eczema. Maintaining basal sweating responses in the finger is the best preventive measures in achieving prevention of dry skin/hand eczema.
Subject(s)
Eczema , Sweating , Humans , Skin , Sweat Glands/physiology , WaterABSTRACT
Cytomegalovirus (CMV) reactivation in patients with autoimmune bullous disease (AIBD) or severe drug eruption treated with immunosuppressive therapy was traditionally thought to be merely an epiphenomenon of the underlying immunosuppression. However, a detailed review of the clinical course of these patients revealed that CMV reactivation occurs upon rapid immune recovery, which is termed immune reconstitution inflammatory syndrome (IRIS), and that the timely initiation of anti-CMV therapy, when combined with maintenance doses of immunosuppressive agents, contributes to a rapid resolution of severe infectious complications thought to be refractory to conventional immunosuppressive therapies and unrelated to CMV reactivation. Thus, CMV reactivation resulting in fatal outcomes (CMV-IRIS) can be prevented by the timely detection of CMV DNA or antigens in the blood and by rapidly starting anti-CMV therapy while maintaining immunosuppressive therapy. Anti-CMV therapy is highly recommended for patients with CMV-IRIS or severe drug eruption who have risk factors for CMV reactivation resulting in fatal outcomes.
ABSTRACT
Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 drives inv(3)/t(3;3) myeloid leukemias via structural rearrangement of an enhancer that upregulates transcription of EVI1. Here, we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 that is frequently present in inv(3)/t(3;3) acute myeloid leukemia (AML) and directly contributes to leukemic transformation. This EVI1 isoform is generated by oncogenic mutations in the core RNA splicing factor SF3B1, which is mutated in >30% of inv(3)/t(3;3) myeloid neoplasm patients and thereby represents the single most commonly cooccurring genomic alteration in inv(3)/t(3;3) patients. SF3B1 mutations are statistically uniquely enriched in inv(3)/t(3;3) myeloid neoplasm patients and patient-derived cell lines compared with other forms of AML and promote mis-splicing of EVI1 generating an in-frame insertion of 6 amino acids at the 3' end of the second zinc finger domain of EVI1. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells, and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21q26) allele resulted in generation of this novel EVI1 isoform in mice and hastened leukemogenesis in vivo. The mutant SF3B1 spliceosome depends upon an exonic splicing enhancer within EVI1 exon 13 to promote usage of a cryptic branch point and aberrant 3' splice site within intron 12 resulting in the generation of this isoform. These data provide a mechanistic basis for the frequent cooccurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).
Subject(s)
Leukemia, Myeloid, Acute , Proto-Oncogenes , Animals , Chromosome Inversion , Chromosomes, Human, Pair 3/metabolism , DNA-Binding Proteins/metabolism , Humans , Leukemia, Myeloid, Acute/pathology , MDS1 and EVI1 Complex Locus Protein/genetics , Mice , Proto-Oncogenes/genetics , Transcription Factors/metabolismABSTRACT
The risk of treating psoriasis with biologic drugs in patients treated with topical corticosteroids over prolonged periods requires careful attention to their underlying adrenal insufficiency because the development of adrenal insufficiency symptoms frequently occurs after cessation of the topical corticosteroids: the dose and duration of topical corticosteroid therapy and etretinate use correlate with risk. In this case report, we present a 65-year-old man with psoriatic erythroderma who developed arthralgia, joint pain, muscle pain, fatigue, and headache after starting brodalumab and a reduction of topical potent corticosteroid doses in the treatment of psoriasis. Because his plasma cortisol levels were decreased and the levels and various signs recovered by administration of physiological doses of hydrocortisone replacement, we concluded that these clinical signs observed after starting brodalumab could be clinical manifestations of adrenal insufficiency secondary to an abrupt reduction in the amount of a topical corticosteroid, but not adverse effects of brodalumab. We found another 2 cases with psoriatic erythroderma who developed secondary to adrenal insufficiency after starting biologic drugs and a reduction of topical corticosteroid doses in the literature. Notably, the side effects of brodalumab include arthralgia, headache, and fatigue, and suspicion of side effects may include the clinical manifestations of adrenal insufficiency. Clinicians have to predict adrenal insufficiency secondary to an abrupt reduction of topical corticosteroids after remarkable improvement of psoriasis by biologics. The routine monitoring of plasma cortisol levels is necessary for all erythrodermic psoriasis patients treated with topical corticosteroids over prolonged periods before starting biologics.
ABSTRACT
Background: Herpes zoster (HZ) occurs mostly in elderly and immunocompromised individuals. Immune reconstitution may be associated with the pathogenesis of HZ. As immune checkpoint inhibitor (ICI) treatment amplifies the immune response, use of ICI may increase the incidence of HZ. There have been few studies of HZ in lung cancer patients treated with ICI. This study was performed to investigate the frequency of HZ in lung cancer patients who received ICI or cytotoxic chemotherapeutic agents. Methods: We searched the electronic medical records for lung cancer patients receiving anticancer drug therapy at our hospital, who developed HZ between April 2011 and June 2020. Results: The review identified 80 patients with a history of ICI treatment (ICI group) and 356 who had been treated with cytotoxic chemotherapeutic agents alone (non-ICI group). Among the 20 patients who developed HZ, 4 (5.0%) belonged to the ICI group and 16 (4.5%) to the non-ICI group (P=0.782). After exclusion of patients aged 65 years and older, to avoid effects of advanced age on the results, the ICI and non-ICI groups consisted of 24 and 81 patients, respectively. In total, 3 of the 24 patients (12.5%) in the ICI group and 1 of the 81 (1.2%) patients in the non-ICI group developed HZ (P=0.0365). Conclusions: There was no significant difference in the rate of HZ between lung cancer patients treated with ICI and those treated with cytotoxic chemotherapy alone. However, patients younger than 65 years treated with ICI might be at increased risk of HZ. Because this is a retrospective small study, further prospective observational studies are needed.
ABSTRACT
Many cases of bullous pemphigoid (BP) have been reported in patients taking dipeptidyl peptidase-4 inhibitors (DPP-4i), which are the most widely used antidiabetic drug for type 2 diabetes mellitus. However, no large-scale survey has been conducted in Japan. This retrospective study investigated the incidence, clinical presentation, and clinical course of DPP-4i-associated BP (DPP-4i-BP) using epidemiological data from a nationwide registry for BP. In 2016, 713 new BP patients at 94 dermatological institutes were registered, 243 (34.1%) with DPP-4i-BP and 461 (64.7%) with non-DPP-4i-BP. The male-to-female ratio was 1.9 and 0.84, respectively. Patients with DPP-4i-BP were predominantly male. Non-inflammatory BP was more common in DPP-4i-BP (33.3%) than in non-DPP-4i-BP (14.6%), while inflammatory BP was common in both. No specific subtype or difference in disease severity was evident in DPP-4i-BP. The most common gliptins administered to DPP-4i-BP patients were vildagliptin (37.2%) and linagliptin (23.8%). DPP-4i intake was discontinued in 79.9% of cases after diagnosis. Some DPP-4i-BP patients (17.6%) achieved spontaneous remission after discontinuing DPP-4i without requiring the use of systemic corticosteroids and/or adjuvant therapy. Mean duration to achieve disease control was 2.87 months. The odds ratio for non-inflammatory BP requiring systemic corticosteroids and/or adjuvant therapy was low (0.52), suggesting that remission was achieved easily with supportive care in that phenotype. Non-inflammatory and mild cases of DPP-4i-BP may resolve spontaneously with supportive care, including the discontinuation of DPP-4i and no oral corticosteroid therapy.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Pemphigoid, Bullous , Adrenal Cortex Hormones/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use , Female , Humans , Hypoglycemic Agents/adverse effects , Japan/epidemiology , Male , Pemphigoid, Bullous/chemically induced , Pemphigoid, Bullous/drug therapy , Pemphigoid, Bullous/epidemiology , Retrospective StudiesABSTRACT
Bullous pemphigoid (BP) is a rare autoimmune blistering disease, and the prevalence of type 2 diabetes mellitus (T2DM) is relatively high in subjects with BP. It is known that dipeptidyl peptidase-4 inhibitor (DPP-4i), one kind of antidiabetic drugs, can cause BP, although precise mechanism of DPP-4i-related BP remains unclear. In this report, we showed a case with appearance of various disease-specific antibodies after the onset of DPP-4i-related BP. Furthermore, various disease-specific antibodies became positive and showed high titers two years after the onset of DPP-4i-related BP and discontinuation of DPP-4i. These data showed that it is possible for immune tolerance to be broken after the onset of DPP-4i-related BP, and it may be important to check autoimmune antibodies in DPP-4i-related BP subjects even when BP symptoms are improved.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Pemphigoid, Bullous , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Humans , Hypoglycemic Agents , Pemphigoid, Bullous/chemically induced , Pemphigoid, Bullous/diagnosis , Pemphigoid, Bullous/epidemiologyABSTRACT
Cholinergic urticaria (CholU)-like rash and dermal pain on sweating occur in patients with acquired idiopathic generalized anhidrosis (AIGA). However, it is unclear whether these are symptoms specific to AIGA among the various types of acquired generalized anhidrosis/hypohidrosis (AGAH). Moreover, the pathogenesis underlying CholU-like rash and dermal pain observed with anhidrosis remains to be clarified. A 20-year-old Japanese man with Sjögren's syndrome (SS) presented with anhidrosis. Transient stinging pain on the skin and pinpoint wheals were observed when his body temperature increased. Thermoregulatory sweat testing revealed anhidrotic areas covering 69% of the body surface area with a symmetrical distribution. A high concentration of histamine was detected (506 ng/mL) in the sweat. A skin biopsy specimen from the anhidrotic area showed the inflamed secretory portion of eccrine glands. This suggested inflammation-mediated damage to sweat glands, consistent with AGAH related to SS. Furthermore, immunohistochemical analysis revealed an ectopic distribution of dermcidin, a sweat-specific peptide, in the dermal tissue surrounding the secretory portion of eccrine glands. The expression of claudin-3, a tight junction (TJ) component of sweat glands, decreased or distributed in a mottled manner in the secretory portion. No decreased expression of muscarinic cholinergic receptor M3 was detected. These results suggested that sweat had leaked into the dermis in association with impaired TJ in the secretory portion, along with the damage to inflamed sweat glands related to SS. Collectively, CholU-like rash and dermal pain on sweating were observed in an AGAH patient with SS. The sweat leakage into the dermis may contribute to the development of the rash and pain.