The impact on the quality of life and sleep complaints in a vitiligo sample and the influence of inflammatory cytokines in the interaction between vitiligo and sleep.

INTRODUCTION: Vitiligo is an autoimmune dermatosis that affects quality of life, which englobes sleep quality. Sleep regulates the immune system, including inflammatory cytokines, and other pathways, which may influence vitiligo pathogenesis. OBJECTIVES: To analyze levels of immune serum components (cytokines) in a vitiligo group, and assess whether there was any association with sleep. METHODS: This study comprised 30 vitiligo patients and 26 control individuals. Quality of life and sleep questionnaires were completed [Dermatology Life Quality Index (DLQI), Short-Form Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)]. Seven cytokines have been measured: IFN-γ, interleukin (IL)-4, IL-6, IL-10, IL-17A, IL-12 p40 and TNF-α. RESULTS: The mean age of the vitiligo group was 47.7 years-old, with prevalence of females (66.7 %). Mucosal (70 %), acral (60 %) and focal subtype (53.3 %) predominated. Signs of vitiligo activity were identified in 63.3 % of the disease sample. Total PSQI scores and scores for domain 4 (sleep efficiency) were statistically worse in vitiligo group. The SF-36 and ISI total scores were worse in the vitiligo group, although not statistically significant compared with controls. Four SF-36 domains were statistically worse in vitiligo sample, and the DLQI mean score was mild to moderate (5.57). Cytokine levels were not different between groups, or when associated with PSQI. Higher ISI scores (more severe insomnia) were related to increased IL-17A. Higher IL-4, IL-6 and IL-10 levels were associated with previous phototherapy. CONCLUSIONS: Poor sleep and impaired aspects of quality of life predominated in the vitiligo sample. Insomnia was related to IL-17A increase in vitiligo. Increased levels of IL-4, IL-6 and IL-10 were related to previous ultraviolet B narrow band (UVB-NB) phototherapy, suggesting an interaction of this treatment on immune system. Sleep disruption and the course of vitiligo may have common pathways in respect of circadian cytokines, which may represent an important subject in vitiligo management.

The relationship between irritable bowel syndrome, the gut microbiome, and obstructive sleep apnea: the role of the gut-brain axis.

Sleep disruption, especially that resulting from obstructive sleep apnea (OSA) - a widely prevalent sleep disorder - can lead to important systemic repercussions. We raise a subject of current interest, namely the possible relationship between sleep in general, OSA, and irritable bowel syndrome (IBS), an intestinal disease that can be made worse by stressful events. The intermittent hypoxia caused by OSA can induce alterations in the gut microbiota, which can lead to the dysregulation of the gut-brain axis and the worsening of IBS. This may be considered to be a circular relationship, with OSA playing a crucial role in the worsening of bowel symptoms, which in turn have a negative effect on sleep. Thus, based on previous evidence, we suggest that improving sleep quality could be a key to disrupting this relationship of IBS aggravation and OSA.

Onychomycosis in immunocompromised population: Phenotypic and molecular identification.

Onychomycosis is common among immunosuppressed individuals. Renal transplant recipients (RTR) and lupus nephritis (LN) patients are submitted to corticosteroid and other immunosuppressive therapy; and diabetes mellitus (DM) patients are intrinsically immunocompromised. OBJECTIVES: The aim of this study was to characterise and identify fungal infections on the nails (feet and hands) in immunocompromised patients. METHODS: The clinical material, nail scales (foot and/or hand), was collected from 47 RTR, 66 LN, 67 DM, and 78 immunocompetent individuals (control group). Phenotypic and molecular analyses were performed. RESULTS: A total of 258 patients were examined. There was a female predominance, except in the RTR. The average age was 52 years old. Lateral distal subungual onychomycosis (OSDL) (75.2%), mainly affecting the hallux nail, was frequent. The predominance of dermatophyte on toenails and Candida species on fingernails was statistically significant. A higher frequency of fingernail involvement in LN and DM, and for LN, the difference was significant (p = .0456). Infections by Candida spp. were more frequent in DM. Using molecular methods, 87.2% of diagnoses were confirmed, identifying fungal agents at the species level. Dermatophytes, Trichophyton rubrum and Trichophyton interdigitale and the species of Candida, C. parapsilosis and C. albicans, were the most frequent fungal agents. CONCLUSIONS: Molecular techniques (sequencing of ITS regions of rDNA) offer greater accuracy, although there is no difference, regarding the detection. Clinical presentation and fungal species may differ somewhat from the general population. Immunosuppression did not increase fungal detection positivity.

Sleep loss and the skin: Possible effects of this stressful state on cutaneous regeneration during nocturnal dermatological treatment and related pathways.

Cutaneous homeostasis can be modulated by sleep. Although there is little evidence about the efficacy of medications topically applied in the morning compared to those administered in the evening, they are commonly prescribed to be used overnight. Poor sleep may affect the tegument, but its repercussion on dermatological therapy is not clear. This communication aims to carry out an overview on the relationship between sleep and the skin, particularly in respect of the effectiveness of topical substances during the night versus the day; and the possible impact of sleep dysregulation on these treatments. Features related to this external organ, involving hydration, blood flow, and the permeability of the superficial barrier have physiological variations in sleep period. Our hypothesis is that sleep loss could alter drug absorption in the dermis and impair the success of the treatment. This can depend on the integrity of the mechanical skin barrier, and the enzymatic process after drug penetration, which may be influenced by the circadian rhythm. We raise the role of sleep disturbance in relation to skin aging and the cutaneous microbiota. The organ integrity and local immunology can be guided by sleep distress, which can modify the control of dermatological diseases. Future comparative analyses are warranted to explore the possible changes of the integumentary system influenced by circadian rhythm, and interference in response to topical dermal treatments. We emphasize the importance of sufficient sleep to improve the clinical management of several dermatosis and cosmetic complaints that need percutaneous therapeutics.

Post-transplant lymphoproliferative disorder with cutaneous involvement: A series of four cases.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are lymphoid proliferations associated with post-transplant immunosuppression. Most originate from B cells and are associated with Epstein-Barr virus (EBV) infection. Although extranodal involvement is common, cutaneous presentation is rare. OBJECTIVE: To report and characterize cutaneous manifestations of PTLD from clinical, histopathologic, and immunohistochemistry standpoints. METHODS: Patients' information was obtained retrospectively by reviewing medical records. Skin biopsies were submitted to histological and immunohistochemistry analysis, and EBV detection was performed by in situ hybridization and polymerase chain reaction (PCR) analysis. Staging examinations were included. A literature review of reported cutaneous PTLD cases was performed. RESULTS: We describe two cases of primary cutaneous and 2 cases of systemic PTLD with secondary cutaneous manifestations. All had late onset disease, which presented at least 6 years after transplantation. Histopathologic findings were compatible with monomorphic PTLD in three cases and plasmacytic hyperplasia in one case. EBV was detected in two patients. Both patients with systemic disease had fatal outcome, and those with primary cutaneous involvement responded to treatment. LIMITATIONS: Due to the rare incidence of cutaneous manifestation of PTLD, the analysis of a large number of cases was not possible. CONCLUSION: Although rare, PTLD should be considered in the differential diagnosis of late onset cutaneous complications post-renal transplant.

Epidemiologic and Clinical Progression of Lobomycosis among Kaiabi Indians, Brazil, 1965-2019.

Lobomycosis is a rare granulomatous skin disease with a high prevalence in the Amazon region. The Kaiabi Indians are an especially affected group. We studied the current epidemiologic and clinical progression of lobomycosis among the Kaiabi in Brazil, from initial case reports in 1965 through 2019. A total of 60 lobomycosis cases had been reported among the Kaiabi, and we identified 3 new cases in our review. Of 550 cases of lobomycosis ever reported worldwide, 11.5% were among the Kaiabi. We note a high incidence among female Kaiabi and a precocious onset of disease in this indigenous population. Male Kaiabi frequently are infected with the multicentric form and women more frequently exhibit the localized form. Ulcerated lesions are observed more often in the multicentric form. The prevalence among this indigenous group could be explained by genetic susceptibility and lifestyle, which exposes them to a particular agent in the habitats in which they live.

Linear verrucous epidermal nevus with oral manifestations: report of two cases.

Linear verrucous epidermal nevi (LVEN) are characterized by verrucous papules often coalescing into well-demarcated skin-colored or brown plaques following the lines of Blaschko. We present two new cases of LVEN with oral mucosa involvement and briefly discuss this very rare finding. In both cases, oral biopsies showed hyperkeratosis, acanthosis, and papillomatosis. Although several treatment modalities have been reported for the cutaneous lesions, there is no consensus for the management of oral lesions so far.

αEß7 Expression Increases With the Extent of Cutaneous Involvement in Mycosis Fungoides.

BACKGROUND: Cell adhesion molecules are essential to lymphocyte migration in neoplastic and inflammatory skin diseases. Our aim was to investigate possible differences in cell adhesion molecule expression between mycosis fungoides (MF) and inflammatory skin diseases (drug reactions and allergic contact dermatitis). METHODS: We selected 33 biopsies from patients with MF and 10 biopsies of patients with inflammatory skin diseases from Department of Pathology-Universidade Federal de São Paulo (UNIFESP) from January 1997 to December 2013. Expression of α4ß1 integrin and αEß7 integrin was assessed by immunohistochemistry in intraepidermal lymphocytes by counting 4 microscopic epidermal fields (×400) and comparing those between the 2 groups. RESULTS: We observed increased expression of integrin αEß7 in intraepidermal lymphocytes in advanced stages of MF (T3 and T4). αEß7 expression was detected in intraepidermal dendritic cells of MF and inflammatory diseases samples. The expression of E-cadherin in epidermal cells in MF outlined Pautrier microabscesses, whereas in inflammatory diseases, spongiosis reduced its expression in keratinocytes. CONCLUSIONS: The findings presented here support the idea that the lymphocyte migratory mechanism observed in neoplasms is similar to that of inflammatory processes of the skin.

Spectral Manifestation of Melanized Fungal Infections in Kidney Transplant Recipients: Report of Six Cases.

Chromoblastomycosis and phaeohyphomycosis are melanized fungal infections, which affect skin and subcutaneous tissues in immunocompetent and immunosuppressed patients, as solid-organ transplant recipients, respectively. In this present study, we report six cases of melanized fungal infection in kidney transplant recipients. In five cases, culture of tissue specimens identified two cases of Exophiala spp. and three cases of Fonsecaea spp. Molecular identification was performed in three cases based on sequencing of rDNA (ITS region) that revealed the following agents: Exophiala xenobiotica, Exophiala bergeri and Fonsecaea monophora. Clinically, they presented verrucous lesion, erythematous-squamous plaque, nodules and lymphangitic distribution. Histopathological aspect was tuberculous granuloma, with concomitant presence of muriform bodies and hyphae. Some patients presented fungal transepithelial elimination. One patient received only terbinafine. Three patients underwent surgery, and two of them received itraconazole. In these four cases, the infection did not relapse. The other two patients were treated only with itraconazole, one of them is still under treatment and the other one was lost to follow-up. These patients presented clinical and histopathological characteristics ranging from resistant to nonresistant forms.

Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil.

BACKGROUND: Evidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and borderline (B) leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B leprosy including borderline-tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL). METHODS: DNA was obtained by the salting-out technique from the blood samples of 202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers. RESULTS: The case-controlled analysis results showed a significant association between B leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20-0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3-0.8, pc = 0.039). A protective association was observed between BL leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15-0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30-5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease. CONCLUSIONS: The results indicate the involvement of HLA class I and class II molecules in B leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.

[Phaeohyphomycosis caused by Colletotrichum gloeosporioides and Alternaría infectoria in renal transplant recipient]. / Feohifomicosis causada por Colletotrichum gloeosporioides y Alternaria infectoria en un paciente trasplantado renal.

Several species of black fungi have been reported as agents of subcutaneous phaeohyphomycosis. Although most of these fungi are considered opportunistic pathogens, they play an important role in phaeohyphomycosis, a disease considered an emergent mycosis among solid organ recipients. We report a case of phaeohyphomycosis caused by Alternaria infectoria of the left hand and the 4th finger of the right hand of a 68-year-old male who underwent a renal transplant 35 months before. The lesion was treated with surgical excision. One year later, the patient presented a new lesion on the 5th finger of the right hand, but this time caused by Colletotrichum gloeosporioides that was also removed surgically. Both lesions did not relapse after being removed. Antifungal susceptibility testing was performed against five antifungal drugs (amphotericin B, itraconazole, flucytosine, fluconazole and voriconazole). Alternaria infectoria was resistant to all five drugs and C. gloeosporioides was sensitive only to amphotericin B and voriconazole. We emphasize the need of histopathologic and microbiologic studies of new lesions of phaeohyphomycosis, since in this case the same patient was infected twice by two different fungi.

Metastasis of skin squamous cell carcinoma in kidney transplant recipients.

Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy in kidney transplant recipients (KTRs) as a result of immunosuppression. A worldwide increase in kidney transplantation justifies the determination of prognostic biomarkers by collecting detailed patient data on metastasis development. This study aims to characterize the clinical, epidemiological, and histopathological profiles of KTRs who developed metastasis of cSCC. We conducted a retrospective single-center study on 18 KTRs and 21 immunocompetent patients (ICs) with metastatic cSCC, using data from 2004 to 2021. ICs were older (median age 70.5 years) than KTRs (median age: 59.5 years). Both groups were predominantly male with Fitzpatrick skin phototype I/II. The primary tumor appeared around 83.5 months post-transplant, usually in sun-exposed areas (61.1%), though some non-exposed areas in ICs (23.8%) contradicted literature findings. KTRs took longer to develop metastasis (median: 11.0 months) compared to ICs (median: 5.5 months). The mean size of the primary tumor was smaller in KTRs (2.50 cm2) compared to ICs (4.55 cm2). The main lymph node chain affected by metastasis was parotid lymph nodes in KTRs (27.8%) and cervical/axillar lymph nodes in ICs (both 19.0%). Both groups exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.

Wade histoid leprosy: histological and immunohistochemical analysis.

Histoid leprosy is a rare multibacillary form that presents with disseminated papule-nodular cutaneous lesions. To study the inflammatory infiltrate of the histoid form and to compare it with other lepromatous forms, we performed histological and immunohistochemical analysis on skin biopsies. Fifteen patients were included for histopathological analysis (10 histoid and five lepromatous) via the haematoxylin-eosin and Ziehl-Neelsen-Faraco stains. Thus, immunohistochemical techniques using immunoperoxidase assay were performed for: anti-BCG, anti-M. leprae, anti-CD8, anti-CD3, anti-CD20, anti-S100, anti-CD1a, anti-CD68 and antivimentin. Spindle cells were present in all histoid patients. A pseudocapsule was observed in half of both studied forms. A comparison using the Ziehl-Neelsen-Faraco stain to evaluate anti-BCG and anti-M.leprae showed no major differences. The CD3+ cells were more pronounced in the histoid form than the lepromatous form. There was greater immunoreactivity toward CD8+ cells in the histoid form, as well as the CD20+ cell count. A similar count of S100+ cells in the epidermis of both leprosy forms was observed. There was a slight increase of dendritic cells in the histoid patients in the superficial and deep dermis. For CD1a marker, we observed expression in the epidermis and superficial dermis in both forms. A diffuse and intense infiltrate of CD68+ cells was also observed in the histoid and lepromatous forms. The high positivity for vimentin did not allow for a positive cell count. We concluded that the activation of both the cellular and humoral response is more pronounced in the histoid form because the T and B cells showed greater infiltration than those in the lepromatous form. The activation of dendritic and Langerhans cells is similar in both forms. The spindle cells likely belong to the macrophage population, thus maintaining phagocytic ability. The quantities of pseudocapsules and bacilli are similar and cannot serve as criteria for diagnosis.

Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study.

INTRODUCTION: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. METHODS: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. RESULTS: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. CONCLUSIONS: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.

Sleep and quality of life in kidney transplant recipients with and without non-melanoma skin cancer: a comparative study.

Non-melanoma skin cancer (NMSC) is prevalent in kidney transplant recipients (KTR), related to the immunosuppressive effects of anti-rejection therapy. Sleep disturbances can alter the immune system and enhance oxidative stress, which may increase the risk of carcinogenesis. This study aimed to analyze the quality of life and sleep in KTR with and without NMSC. Participants answered a set of questionnaires, the WHOQOL-bref, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Berlin Questionnaire and self-reported chronotype. The total sample was distributed in the following groups: KTR with NMSC (n = 42), KTR without NMSC (n = 43) and healthy controls (n = 41). The mean scores of the questionnaires were not statistically significant, except for 3 domains of PSQI (sleep quality, sleep latency and daily consequences of poor sleep). The KTR with NMSC and control group presented worse sleep quality. Worse sleep latency and more daytime consequences were found in KTR groups. All groups had a numerical predominance of low-quality sleep (PSQI) and greater sleepiness (EES). Higher risk of obstructive sleep apnea was not observed and the evening-type chronotype was most frequent. In the WHOQOL, compromised physical domain was observed in KTR. Significant results were reached in few aspects of quality of life and sleep comparing KTR and controls. All groups presented excessive daytime sleepiness and low-sleep quality.