RESUMO
Linear IgA disease (LAD) is a rare autoimmune bullous disease characterized by IgA deposition in the basement membrane zone (BMZ). A 66-year-old male was treated for myelodysplastic syndrome at our hospital for 5 years, during which his condition remained stable. He visited our department because of erythema with itching, which appeared 1 year ago and gradually exacerbated with the development of blisters and erosions. During the first visit, multiple erythemas with erosions and crusts on their periphery were observed on the trunk and lower limbs. Histopathological examination revealed subepidermal blisters with inflammatory cell infiltration, mainly constituting of neutrophils, eosinophils, and lymphocytes. Direct and indirect immunofluorescence showed linear IgA deposits in the BMZ and IgA anti-BMZ antibodies, respectively, while immunoblotting using a concentrated culture supernatant of HaCaT cells detected IgA antibodies reactive to 120-kDa LAD-1. Accordingly, the patient was diagnosed with lamina lucida-type LAD. Subsequent colonoscopy revealed multiple colorectal polyps and rectal adenocarcinoma (Tis, N0, and M0). Multigene panel test showed an ATM variant of unknown significance but did not detect any pathogenic variants associated with intestinal polyposis syndrome. The skin lesions quickly resolved with oral diaphenylsulfone 50 mg/day and resection of the colorectal polyps and adenocarcinoma. To our knowledge, this is the first reported case of LAD associated with multiple colorectal polyps and rectal adenocarcinoma. Additionally, we also analyzed reported cases of LAD associated with malignancy from the literature.
RESUMO
RATIONALE: Basal cell carcinoma (BCC) arising in the umbilicus is relatively rare, and in particular, there have been few reports mentioning peritumoral sweat gland structures histopathologically. We herein, report 2 cases of umbilical BCC with sweat gland structures within and around the tumor. PATIENT CONCERNS: A 61-year-old woman had a 2-year history of black exudative plaque in her umbilicus, and an 80-year-old woman had a 6-month history of dark brownish plaque in the umbilicus, with exudation 2 months prior to her first visit. DIAGNOSES: Based on the histopathological finding, both cases were confirmed as BCC. The results of immunohistochemical staining showed that the tumor cells were Ber-EP4 positive. In addition, EMA-positive glandular structures were seen within and around the tumor. INTERVENTIONS: Curative resection at the level of the linea alba on the bottom side was performed. OUTCOMES: No relapse has been observed since resection in either patient. LESSONS: We herein report 2 cases of umbilical BCC with sweat glands and ducts. Although whether peri- and/or intra-tumor sweat gland structures are the source of the tumor or arise by transdifferentiation from tumor cells remains unclear, these findings may provide clues to help understand the morphopathogenesis of umbilical BCC in the future.
Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/patologia , Umbigo/patologia , Recidiva Local de Neoplasia/patologia , Carcinoma Basocelular/patologia , Glândulas Sudoríparas/patologiaRESUMO
Immune checkpoint inhibitors (ICI), including monoclonal antibodies to programmed death 1, programmed death ligand 1, and cytotoxic T lymphocyte-associated antigen 4, have provided great therapeutic benefits for cancer patients at advanced stages. However, the introduction of ICI frequently results in the development of immune-related adverse events (irAE) through activation of autoreactive T cells. Here, we present three cases of cancer patients with cutaneous irAE, including development of de novo psoriasis and exacerbation of pre-existing psoriasis. Interestingly, these patients shared an altered histological feature characterized by loss of epidermal CD1a+ cells, namely Langerhans cells (LC), in the psoriasiform lesions in contrast to "conventional psoriasis" exhibiting unchanged or activated LC. A possible underlying mechanism was that ICI-mediated hyperactivation of effector T cells contributed to aggravation or establishment of psoriasis phenotype, which might be associated with direct cytotoxicity or expulsion of LC from the epidermis.
Assuntos
Antineoplásicos Imunológicos , Neoplasias , Psoríase , Antineoplásicos Imunológicos/efeitos adversos , Humanos , Inibidores de Checkpoint Imunológico , Células de Langerhans , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológicoRESUMO
Pediatric cutaneous mastocytosis (CM) is mainly attributed to gain-of-function mutations in KIT in mast cells. On the other hand, growing evidence suggests that CM patients exist without KIT mutations. To date, the association between the KIT mutation status and clinical phenotype has not been elucidated in pediatric CM, especially in patients with wild-type KIT. Nevertheless, genetic analysis has yet to be performed with whole KIT sequence of mast cells in Japanese patients with pediatric CM. In the present study, 11 Japanese patients with pediatric CM were analyzed to determine whether they had KIT mutations in their skin, and their clinical phenotypes were observed. The approximate frequency of patients with KIT mutation and that of wild-type KIT was almost consistent with the European analysis. The distribution of overall macules was similar between the patients with and without KIT mutations.
Assuntos
Estudos de Associação Genética , Mastocitose Cutânea/genética , Proteínas Proto-Oncogênicas c-kit/genética , Pré-Escolar , Análise Mutacional de DNA , Feminino , Mutação com Ganho de Função , Humanos , Lactente , Recém-Nascido , Masculino , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/patologia , Pele/citologia , Pele/patologiaAssuntos
Dermatite Alérgica de Contato/diagnóstico , Toxidermias/diagnóstico , Dermatoses Faciais/diagnóstico , Ureia/análogos & derivados , Dermatite Alérgica de Contato/etiologia , Diagnóstico Diferencial , Toxidermias/etiologia , Dermatoses Faciais/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Testes do Emplastro/métodos , Medição de Risco , Ureia/efeitos adversos , Ureia/imunologiaRESUMO
We experienced a rare case of drug-induced hypersensitivity syndrome (DIHS) in which salazosulfapyridine (SASP) reactivated human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), which resulted in a relapse of skin symptoms after changing to mizoribine. At the time of recurrence of skin erythema after the initiation of mizoribine, the serum DNA titers of not HHV-6 but CMV were elevated. A drug-induced lymphocyte stimulation test was negative for mizoribine but positive for SASP. In this case, DIHS developed with SASP in association with HHV-6 and CMV reactivation. The immunocompromised state induced by herpes virus reactivation and mizoribine might have caused the relapse of skin erythema.
RESUMO
Keratinocytes are known to synthesize cortisol through activation of the enzyme 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1). To confirm the function of 11ß-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific-11ß-HSD1 knockout mice (K5-Hsd11b1-KO mice) and analyzed the response to narrow-band ultraviolet B (NB-UVB) irradiation. Firstly, we measured the mRNA and protein levels of 11ß-HSD1 following NB-UVB irradiation and found that the expression of 11ß-HSD1 in keratinocytes of mouse ear skin was enhanced at 3 and 24 hours after 250 mJ/cm(2), 500 mJ/cm(2), 1 J/cm(2), and 2 J/cm(2) NB-UVB irradiation. Next, we determined that 24 hours after exposure to 1 J/cm(2) NB-UVB irradiation, the numbers of F4/80-, CD45-, and Gr-1-positive cells were increased in K5-Hsd11b1-KO mice compared to wild type (WT) mice. Furthermore, the expression of the chemokine (C-X-C-motif) ligand 1 (CXCL1) and interleukin (IL)-6 was also significantly enhanced in NB-UVB-irradiated K5-Hsd11b1-KO mice compared with WT mice. In addition, activation of nuclear factor-kappa B (NF-κB) after NB-UVB irradiation was enhanced in K5-Hsd11b1-KO mice compared to that in WT mice. Thus, NB-UVB-induced inflammation is augmented in K5-Hsd11b1-KO mice compared with WT mice. These results indicate that 11ß-HSD1 may suppress NB-UVB-induced inflammation via inhibition of NF-κB activation.
RESUMO
Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction.