Benznidazole-induced drug reaction with eosinophilia and systemic symptoms syndrome in a patient with human leucocyte antigen (HLA)-A*68.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe drug hypersensitivity reaction with potentially life-threatening consequences. It is characterised by fever, extensive maculopapular exanthema, lymph node enlargement, abnormal blood cell counts, and organ-related complications. Diagnosis can be challenging due to incomplete or non-specific symptoms, and it can sometimes manifest as a purely systemic disease. Discontinuation of the causative drug is essential. Treatment may involve corticosteroids and supportive care. Genetic screening for specific markers, such as human leucocyte antigen (HLA)-A*68, A11:01, and A29:02, can help identify individuals at risk for severe reactions to benznidazole, a drug used to treat Chagas disease. This case report describes the rarity and severity of DRESS syndrome, underscoring the potential benefit of genetic screening to prevent adverse reactions in patients with Chagas disease.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Coexistence of junctional epidermolysis bullosa, autosomal recessive deafness type 57, and Angelman syndrome: A case report.

Key Clinical Message: The presence of more than one genetic/genomic disorder is not uncommon. It is therefore essential to continuously consider new signs and symptoms over time. Administration of gene therapy could be extremely difficult in particular situations. Abstract: A 9-month-old boy presented to our department for evaluation of developmental delay. We found that he was affected by intermediate junctional epidermolysis bullosa (COL17A1, c.3766 + 1G > A, homozygous), Angelman syndrome (5,5 Mb deletion of 15q11.2-q13.1), and autosomal recessive deafness type 57 (PDZD7, c.883C > T, homozygous).

Esophageal lichen planus: an unusual case of dysphagia.

An unusual case of chronic dypshagia associated with impaired quality of life in a 73-years old patient with past medical history of tongue squamous cell carcinoma. Prior esophagogastroduodenoscopy (EGD) with formalin-fixed biopsies has demonstrated inespecific findings. A few months later, new EGD was performed and esophageal stricture with sloughed mucosa was shown. With formaline and fresh biopsies was made the diagnosis of esophageal lichen planus. With medical treatment and dilations the patient had a good outcome. This is an underdiagnostic disease that has been associated with squamous cell carcinoma and impair quality of life due to the dysphagia. Immunohistochemistry can be useful for diagnosis and fresh biopsies should be considered to increase diagnostic sensitivity.

Skin Manifestations in Patients with Selective Immunoglobulin E Deficiency.

Selective immunoglobulin E deficiency (SIgED) is still an unrecognised primary immunodeficiency despite several observations supporting its existence. This study aimed to describe the skin manifestations associated with SIgED. We retrospectively assessed medical records of patients with SIgED, the diagnosis being based on serum IgE levels ≤2 Uk/L associated with normal serum levels of immunoglobulins G, M, and A. A total of 25 patients (24 female) with SIgED were included in the study. Eleven patients (44%) presented chronic spontaneous urticaria (CSU), five (20%) angioedema always associated with CSU, five erythema (20%), and six eczema (24%). Other, less frequent manifestations were lichen planus, anaphylactoid purpura, thrombocytopenic purpura, bullous pemphigoid, bullous pyoderma gangrenosum, and atypical skin lymphoproliferative infiltrate associated with reactive lymphadenopathy, chronic cholestasis, arthritis, and fibrosing mediastinitis. Fifteen patients (60%) had different types of associated autoimmune diseases, Hashimoto's thyroiditis being the most frequent (n = 5, 20%), followed by arthritis (n = 4, 16%), autoimmune hepatitis, neutropenia, vitiligo, and Sjögren's syndrome (n = 2, 8% each). Five malignancies were diagnosed in four patients (16%). An ultralow IgE serum level may be the only biomarker that reveals the presence of a dysregulated immune system in patients with a broad spectrum of skin manifestations.

Clinical and molecular response to dasatinib in an adult patient with Penttinen syndrome.

Penttinen type of premature aging syndrome is an autosomal-dominant disorder that can be caused by the c.1994T>A pVal665Ala pathogenic variant in platelet-derived growth factor receptor-B (PDGFRB). Imatinib, a receptor tyrosine kinase (RTK) inhibitor, has been used in Penttinen syndrome (PS) patients with good results. A 21-year-old male presented shortly after birth with a prematurely aged appearance with distinctive facial features and cutaneous atrophy with hypertrophic scar-like lesions. Generalized brachydactyly with acro-osteolysis was observed. Flexion contractures limited his daily activities. Cognitive impairment was not present. Genetic testing found a heterozygous variant c.1994T>A pVal665Ala in exon 14 of PDGFRB. A diagnosis of PS was made and imatinib treatment was started with partial response. After lack of further improvement, in vitro molecular studies with imatinib and dasatinib showed that the Val665Ala variant had greater sensitivity to dasatinib than imatinib. This was seen examining levels of P-PDGFRB directly and on downstream ligands P-AKT and P-STAT. Improved clinical response was observed after treatment with dasatinib. We report a new case of PS with clinical and molecular response to dasatinib after incomplete response to imatinib. Our work provides further molecular and clinical evidence of RTK inhibitors' efficacy in this rare disorder.

High-Frequency Ultrasound to Assess Activity in Connective Tissue Panniculitis.

Determining disease activity from clinical signs in patients with connective tissue panniculitis (CTP) is often challenging but is essential for therapeutic decision making, which largely relies on immunosuppressant treatment. High-frequency ultrasound (HFUS) may be useful in supporting such decisions by accurately determining CTP activity. This study aimed to investigate the accuracy of HFUS in identifying signs of CTP activity or inactivity and assess its usefulness in therapeutic decision making. A prospective cohort study of consecutive patients with biopsy-proven CTP receiving HFUS was conducted in a tertiary university hospital (2016-2020). HFUS was performed at inclusion and at each 3- or 6-month follow-up visit, depending on disease activity. Twenty-three patients with CTP were included, and 134 HFUSs were performed. In 59.7% (80) of the evaluations, the clinical presentation did not show whether CTP was active or not. In these cases, HFUS showed activity in 38.7% (31) and inactivity in 61.3% (49). In 71.25% (57) of the visits, HFUS was the determinant for therapeutic decisions. Further follow-up showed consistent clinical and HFUS responses in all unclear cases after treatment modification. HFUS appears to be a useful adjunct to the clinical examination for CTP to assess activity and make therapeutic decisions.

Spectrum of Disease Manifestations in Patients with Selective Immunoglobulin E Deficiency.

BACKGROUND: Selective IgE deficiency (SIgED) has been previously evaluated in selected patients from allergy units. This study investigates the effects of SIgED on the entire population in a hospital setting and sought to delineate in detail the clinical aspects of SIgED. METHODS: A retrospective study of the data obtained from electronic medical records of 52 adult patients (56% female) with a mean age of 43 years and IgE levels of <2.0 kU/L with normal immunoglobulin (Ig) IgG, IgA, and IgM levels, seen at our hospital, without selection bias, from 2010 to 2019. RESULTS: Recurrent upper respiratory infections were recorded in 18 (34.6%) patients, pneumonia was recorded in 16 (30.7%) patients, bronchiectasis was recorded in 16 (30.7%) patients, and asthma was recorded in 10 (19.2%) patients. Eighteen patients (34.6%) suffered autoimmune clinical manifestations either isolated (19%) or combining two or more diseases (15%), Hashimoto's thyroiditis being the most frequent (19%), which was followed by arthritis (10%) and thrombocytopenia and/or neutropenia (5.7%). Other less frequent associations were Graves' disease, primary sclerosing cholangitis, Sjögren's syndrome, and autoimmune hepatitis. Eczematous dermatitis (15.3%), chronic spontaneous urticaria (17.3%), and symptoms of enteropathy (21%) were also highly prevalent. Thirty percent of patients developed malignancies, with non-Hodgkin lymphomas (13.4%) being the most prevalent. CONCLUSIONS: The clinical manifestations of SIgED encompass a variety of infectious, non-infectious complications, and malignancy. Since it cannot be ruled out that some type of selection bias occurred in the routine assessment of IgE serum Ievels, prospective studies are required to better characterize SIgED and to determine whether it should be added to the list of antibody deficiencies.

Assessment of Sclerodermoid Chronic Graft-versus-host Disease with Colour Doppler Ultrasound.

Sclerodermoid chronic graft-versus-host disease (scGVHD) is a severe complication of allogeneic haema-- topoietic stem cell transplantation. The aim of this study was to investigate the usefulness of high-frequency ultrasound of the skin in assessing the inflammatory patterns and prognosis of patients with scGVHD. A prospective study was carried out with patients who developed scGVHD in the period June 2016 to April 2018. Clinical and ultrasound examinations were performed on the first visit and at 6-month follow-up. A total of 24 patients were included in the study. A 6-month follow-up high-frequency ultrasound of the skin was performed on 20 of the 24 patients. Abnormal B-mode findings in high-frequency ultrasound of the skin consisted of hypoechogenic dermis, hypoechogenicity of septa and hyperechogenicity of lobules in hypodermis. No differences were observed in these basal parameters between treatment progressive/non-responding and inactive/responding scGVHD groups of patients. Basal Doppler showing increased vascular flow with a systolic peak ≥10 cm/s and a vascular resistance index ≥ 0.70 was observed only in those patients who developed progressive/non-responding scGVHD (62.5% vs 0% p = 0.006). In conclusion, Doppler ultrasound is a useful tool to assess the inflammatory activity and outcome of scGVHD. These findings could enhance patient management and help to guide treatment decisions.

Cutaneous infection by Phaeoacremonium parasiticum / Infección cutánea por Phaeoacremonium parasiticum

Background: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. Case report: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding β-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. Conclusions: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown

Antecedentes: Phaeoacremonium parasiticum es considerado un agente infeccioso poco común que forma parte de un grupo heterogéneo de hongos causantes de feohifomicosis. Este microorganismo es capaz de producir infección cutánea, eumicetoma, osteomielitis, artritis, miositis e incluso enfermedad diseminada como fungemia y endocarditis. Caso clínico: Se describe un caso de infección cutánea por P. parasiticum en un paciente trasplantado renal. Para la identificación del microorganismo se realizaron pruebas microbiológicas e histopatológicas, y se confirmó la identificación con la secuenciación del gen de la β-tubulina y una PCR a tiempo real para la detección del gen 18S rRNA. El microorganismo fue identificado correctamente por métodos fenotípicos y moleculares. El paciente recibió tratamiento con antifúngicos orales y citorreducción quirúrgica, y evolucionó sin ninguna complicación. Conclusiones: El diagnóstico de esta infección es difícil y se presenta habitualmente en pacientes trasplantados renales. Sin embargo, la asociación de esta infección con este tipo de pacientes no ha sido aún explicada

Clinical and Dermoscopic Evaluation of Melanocytic Lesions in Patients with Chronic Graft Versus Host Disease.

Patients treated with haematopoietic stem cell transplantation are at increased risk of cutaneous malignant neoplasms. There are no reports on the characteristics of melanocytic lesions in patients with chronic graft versus host disease and the value of recognizing these difficult lesions in high-risk patients. The objective of this study is to describe the clinical and dermoscopic characteristics of melanocytic lesions in patients with chronic graft versus host disease in order to understand their morphology. A prospective cross-sectional study was performed; 10 melanocytic lesions on the trunk and extremities were selected from each patient. A statistically significant association was found between regression and high total dermoscopic score and 7-point checklist score. Lesions were excised or included in short-term digital follow-up. Melanocytic lesions in patients with chronic graft versus host disease developing after allogeneic-haematopoietic stem cell transplantation exhibit marked structural and colour changes similar to melanoma. This is believed to result from the inflammatory process associated with graft versus host disease.

Cutaneous infection by Phaeoacremonium parasiticum.

BACKGROUND: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. CASE REPORT: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding ß-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. CONCLUSIONS: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown.