Clinical, tomographic and functional comparison of sporadic and tuberous sclerosis complex-associated forms of lymphangioleiomyomatosis: a retrospective cohort study.

Background: Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function. Methods: This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM. Results: Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM. Conclusion: Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

Hereditary epidermolysis bullosa: clinical-epidemiological profile of 278 patients at a tertiary hospital in São Paulo, Brazil.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare hereditary diseases, characterized by fragility of the skin and mucous membranes. Epidemiological data on EB in Brazil are scarce. OBJECTIVES: To describe epidemiological aspects of patients with EB diagnosed in the Dermatology Department of a tertiary hospital, from 2000 to 2022. METHODS: An observational and retrospective study was conducted through the analysis of medical records. The evaluated data included clinical form, sex, family history, consanguinity, age at diagnosis, current age, time of follow-up, comorbidities, histopathology and immunomapping, presence of EB nevi and squamous cell carcinomas (SCC), cause of and age at death. RESULTS: Of 309 patients with hereditary EB, 278 were included. The most common type was dystrophic EB (DEB), with 73% (28.4% dominant DEB, 31.7% recessive DEB and 12.9% pruriginous DEB). Other types were junctional EB with 9.4%, EB simplex with 16.5% and Kindler EB with 1.1%. Women accounted for 53% and men for 47% of cases. Family history was found in 35% and consanguinity in 11%. The mean age at diagnosis was 10.8 years and the current age was 26 years. The mean time of follow-up was nine years. Esophageal stenosis affected 14%, dental alterations affected 36%, malnutrition 13% and anemia 29%. During diagnostic investigation, 72.6% underwent histopathological examination and 92% underwent immunomapping. EB nevi were identified in 17%. Nine patients had SCC. Eleven patients died. STUDY LIMITATIONS: Insufficient data included to medical records, loss to follow-up, and unavailability of genetic testing. CONCLUSIONS: In this study, dystrophic EB predominated and the need for multidisciplinary care for comorbidities and complications was highlighted.

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

BACKGROUND: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). OBJECTIVE: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. METHODS: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. RESULTS: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. STUDY LIMITATIONS: Small sample size and limited length of follow-up. CONCLUSIONS: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.

Pediatric dermatoses pattern at a Brazilian reference center.

OBJECTIVE: The aim of this study was to identify the pattern of pediatric dermatoses of patients evaluated at a dermatologic clinic of a reference center in Brazil and to compare these results to similar surveys conducted in other countries. METHODS: A retrospective study was performed of patients up to 18 years old, evaluated at a dermatologic clinic between January 1, 2017 and December 31, 2017. Variables collected for analysis included age, gender, dermatological diagnosis, multidisciplinary follow-up, hospitalization, and complementary exams. RESULTS: A total of 2330 patients were included for analysis, with a mean age of 9.7 years. 295 patients were diagnosed with more than one skin disease, leading to a total of 2668 diagnoses. Skin diseases were organized into categories and inflammatory dermatoses corresponded to the largest group (31.2%), mostly due to atopic dermatitis (18.3%). The other main categories were: genodermatoses (14.2%), infectious diseases (12.6%), adnexal disorders (12.5%), cysts and neoplasms (10.7%), and vascular disorders (7.0%). Fifty-six patients needed to be admitted to the dermatology ward; 25 of them (44.6%) for management of worsening of the skin disease, mainly atopic dermatitis, psoriasis, and drug reactions. There were 885 biopsies performed in 38.0% of the subjects and 751 patients (32.2%) required multidisciplinary care; most of them had some genodermatoses. CONCLUSIONS: Dermatologic disorders are very common in the pediatric age group and differ from those in adults, suffering influence from cultural, ethnic, socioeconomic, and environmental factors. Knowing the magnitude and distribution of these dermatoses is important to better plan healthcare policies.

PHACE syndrome: clinical manifestations, diagnostic criteria, and management.

Infantile hemangioma can be linked to other organ malformations. In 1996, PHACE syndrome was first defined as the association of large and segmental infantile hemangioma, usually on the face, head, or cervical region, with malformations of the posterior fossa of the brain, arterial anomalies of the central nervous system, coarctation of the aorta, cardiac defects, and ocular abnormalities. Over 300 cases of PHACE syndrome have been reported, and it is cconsidered one of the most common neurocutaneous vascular disorders in childhood. Knowledge of the features and locations of lesions that imply a greater risk of systemic involvement is crucial for the diagnosis and proper management of PHACE syndrome patients. This review highlights the diagnostic criteria for PHACE syndrome, the imaging workup for extracutaneous involvement, the treatment of infantile hemangioma, and the importance of a multidisciplinary approach in the management of these patients.

Tuberous sclerosis complex: review based on new diagnostic criteria.

Tuberous sclerosis complex is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as skin, central nervous system, kidney and lung. Due to the wide phenotypic variability, the disease is often not recognized. Tuberous sclerosis complex affects one in 10,000 newborns and most patients are diagnosed during the first 15 months of life. The diagnostic criteria for tuberous sclerosis were reviewed in 2012, at the second International Tuberous Sclerosis Complex Consensus Conference. The diagnosis is based on genetic criteria, by the identification of inactivating pathogenic mutation of tumor suppressor genes TSC1 and TSC2, and clinical criteria, including cutaneous, renal, pulmonary, cardiac and neurological manifestations. The treatment of tuberous sclerosis complex consists, mainly, in management of the symptoms caused by hamartomas and in prevention of organ failure. Multidisciplinary approach is recommended, in order to obtain better clinical outcomes.

PHACE syndrome: clinical manifestations, diagnostic criteria, and management

Abstract: Infantile hemangioma can be linked to other organ malformations. In 1996, PHACE syndrome was first defined as the association of large and segmental infantile hemangioma, usually on the face, head, or cervical region, with malformations of the posterior fossa of the brain, arterial anomalies of the central nervous system, coarctation of the aorta, cardiac defects, and ocular abnormalities. Over 300 cases of PHACE syndrome have been reported, and it is cconsidered one of the most common neurocutaneous vascular disorders in childhood. Knowledge of the features and locations of lesions that imply a greater risk of systemic involvement is crucial for the diagnosis and proper management of PHACE syndrome patients. This review highlights the diagnostic criteria for PHACE syndrome, the imaging workup for extracutaneous involvement, the treatment of infantile hemangioma, and the importance of a multidisciplinary approach in the management of these patients.

Tuberous sclerosis complex: review based on new diagnostic criteria

Abstract: Tuberous sclerosis complex is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as skin, central nervous system, kidney and lung. Due to the wide phenotypic variability, the disease is often not recognized. Tuberous sclerosis complex affects one in 10,000 newborns and most patients are diagnosed during the first 15 months of life. The diagnostic criteria for tuberous sclerosis were reviewed in 2012, at the second International Tuberous Sclerosis Complex Consensus Conference. The diagnosis is based on genetic criteria, by the identification of inactivating pathogenic mutation of tumor suppressor genes TSC1 and TSC2, and clinical criteria, including cutaneous, renal, pulmonary, cardiac and neurological manifestations. The treatment of tuberous sclerosis complex consists, mainly, in management of the symptoms caused by hamartomas and in prevention of organ failure. Multidisciplinary approach is recommended, in order to obtain better clinical outcomes.

Sweet Syndrome: Clinical Features, Histopathology, and Associations of 83 Cases.

BACKGROUND: Sweet syndrome (SS) is an infrequent skin disease characterised by sudden onset of fever, leukocytosis, neutrophilia, and tender erythematous plaques infiltrated by neutrophils. Multiple conditions have been associated with this syndrome. OBJECTIVES: The aim of this study was to evaluate the clinical, epidemiological, laboratory, and histopathological findings and associations of patients with SS. METHODS: We conducted a retrospective study of 83 patients with SS followed between January 1, 2006, and January 31, 2015. RESULTS: Of the patients, 82% were female; the mean age at onset was 48 years. Clinical presentation was mainly characterised by erythematous and edematous plaques, mostly on upper extremities and trunk. Fever was observed in 32%; 60% presented leukocytosis and 39% neutrophilia. On histopathological examination, neutrophilic and lymphohistiocytic infiltrate and edema were the most frequent findings. Fourteen percent of patients had malignancy or hematologic disorders, 26% were classified as having drug-induced SS, and 24% noted recent infection. Only 2 cases occurred during pregnancy. Systemic corticosteroid was the most common choice of treatment, with excellent response. In malignancy-associated SS, the mean hemoglobin level was lower ( P = .01) and the erythrocyte sedimentation rate (ESR) was higher ( P = .04) in comparison to classic and drug-induced SS. Leukocytoclasia was associated with higher risk of recurrence ( P = .01). CONCLUSION: All patients with SS deserve careful investigation of possible underlying conditions. Higher ESR and lower hemoglobin levels might reinforce the need of malignancy screening. Also, leukocytoclasia appears to be a potential marker of higher recurrence rate, demanding closer and longer follow-up.

Ultrasonography as an objective tool for assessment of infantile hemangioma treatment with propranolol.

BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. Propranolol is an effective drug in treating IH. A reliable and complementary instrument is necessary to evaluate IH response to propranolol in addition to clinical and photographic assessments. Ultrasonography is a simple and non-invasive technique that enables precise measurements of tumor size and contributes to objective follow-up. OBJECTIVE: To demonstrate the use of serial ultrasonography as an adjunctive tool for assessment of IH treatment with propranolol. PATIENTS AND METHODS: A retrospective study of 19 patients with IH treated with propranolol was conducted from January 2009 to March 2014. Data of individual IH volume at the beginning and at least 6 months after the onset of treatment and overall volume reduction by ultrasonographic measurement were obtained. RESULTS: We observed a statistically significant IH volume reduction of approximately 0.51 cm3 . This volume corresponds to an average reduction of 47% in the final volume compared with the initial volume. CONCLUSION: Ultrasonographic measurements contribute to demonstrate tumor regression and IH response to propranolol. Thus, ultrasonography is an important instrument to guide therapeutic strategies.

Skin barrier in atopic dermatitis: beyond filaggrin.

Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Skin barrier in atopic dermatitis: beyond filaggrin

Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Profile of patients admitted to a triage dermatology clinic at a tertiary hospital in São Paulo, Brazil.

BACKGROUND: Knowledge of epidemiological data on skin diseases is important in planning preventive strategies in healthcare services. OBJECTIVE: To assess data from patients admitted to a triage dermatology clinic. METHODS: A retrospective study was performed of patients admitted over a one-year period to the Triage Dermatology Clinic at the Hospital das Clínicas of the University of São Paulo Medical School. Data were obtained from record books. The variables analyzed were: patient age, gender, dermatologic disease (initial diagnosis), origin (from where the patient was referred) and destination (where the patient was referred to). RESULTS: A total of 16,399 patients and 17,454 diseases were identified for analysis. The most frequent skin disorders were eczema (18%), cutaneous infections (13.1%), erythematous squamous diseases (6.8%) and malignant cutaneous neoplasms (6.1%). Atopic dermatitis was the most common disease in children. Acne was more common among children and adults, as were viral warts. Basal cell carcinoma and squamous cell carcinoma were more common in the elderly. Contact dermatitis and acne predominated in women. The most frequent origins were: the primary/secondary health system (26.6%), other outpatient specialties (25.5%), emergency care (14.9%); while the destinations were: discharged (27.5%), follow-up in our Dermatology Division (24.1%), return (14.1%) and the primary/secondary health system (20.7%). CONCLUSION: Understanding the incidence of skin diseases is fundamental in making decisions regarding resource allocation for clinical care and research. Thus, we believe our findings can contribute to improving public health policies.