MOHS micrographic surgery for head and neck nonmelanoma skin cancer: An approach for ENT surgeons.

Surgery is the main approach for skin cancer, with Mohs micrographic surgery (MMS) allowing the highest cure rates, best esthetics and superior functional outcomes. Ear, nose, and throat (ENT) surgeons are often challenged with patients presenting skin cancer, needing appropriate expertise to its adequate management. This paper highlights the most important aspects of MMS, enabling ENT surgeons to become familiar with its fundamental aspects. A review of the literature was performed, concomitantly presenting the author's outcomes as an ENT surgeon. A total of 51 MMSs were performed in 41 patients, and 78.4% of the tumors were cutaneous basal cell carcinomas (cBCCs), 19.6% were cutaneous squamous cell carcinomas (cSCCs), and one case was a microcystic adnexal carcinoma. Most tumors were located in high-risk areas (88.2%), and 84.3% of them were ≥10 mm in diameter. Most tumors (90.2%) required no more than two MMS excision steps to be completely removed. All cases were managed by reconstruction either using flaps or grafts. Recurrence occurred in only 2% of the cases. This study addressed the main issues of MMS, which may be important in ENT surgeons' daily practice.

Solitary nodule on the shoulder of an 11-year-old child.

Plexiform fibrohistiocytic tumor is an uncommon soft tissue neoplasm of intermediate malignancy, most frequently occurring as a painless, slow-growing nodule that shows a distinct predilection for children and young adults. We report a healthy 11-year-old boy presenting with a 1-year history of an asymptomatic cutaneous nodule on his left shoulder. Histopathological and immunohistochemical analysis confirmed a diagnosis of plexiform fibrohistiocytic tumor. Despite following a usually benign clinical course, this neoplasm is prone to frequent local recurrence and occasional metastatic ability. It should be considered in the differential diagnosis of an enlarging nodule in pediatric patients.

Synthesis, Structure, Properties, and Bioimaging of a Fluorescent Nitrogen-Linked Bisbenzothiadiazole.

This paper describes the synthesis, structure, photophysical properties, and bioimaging application of a novel 2,1,3-benzothiadiazole (BTD)-based rationally designed fluorophore. The capability of undergoing efficient stabilizing processes from the excited state allowed the novel BTD derivative to be used as a stable probe for bioimaging applications. No notable photobleaching effect or degradation could be observed during the experimental time period. Before the synthesis, the molecular architecture of the novel BTD derivative was evaluated by means of DFT calculations to validate the chosen design. Single-crystal X-ray analysis revealed the nearly flat characteristics of the structure in a syn conformation. The fluorophore was successfully tested as a live-cell-imaging probe and efficiently stained MCF-7 breast cancer cell lineages.

Cutaneous Richter Syndrome mimicking a lower limb cellulitis infection - a case report and review of the literature.

Richter syndrome (RS) is characterized by the development of a high-grade lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Herein, we present the case of an 85-year-old woman with a 3-year history of stable asymptomatic CLL that developed a cutaneous RS. The patient presented with painless inflammation in the left leg and foot that was initially diagnosed as a cellulitis infection. She was treated accordingly with ceftriaxone and clindamycin. However, after completing the antibiotic regimen, not only did the inflammation persist, but also superimposed painless nodules gradually appeared on the left leg and foot over the course of four months. The histopathological examination of the nodules revealed a large B-cell cutaneous lymphoma. The patient underwent chemotherapy with CVP, followed by R-CHOP, resulting in a reduction of size of the nodules and remission of the inflammation. The patient died five months after the diagnosis owing to a bacterial pneumonia. We identified in previous reports a total of fifteen cases of cutaneous RS. Most cases presented with rapidly growing tumors or multiple erythematous nodules, similar to our case. This case of a cutaneous RS mimicking a cellulitis infection underlines the importance of a low threshold for performing biopsies of suspicious skin lesions in patients with CLL/SLL.

Dupilumab in Patients with Atopic Dermatitis: A Multicentric, Long-Term, Real-World Portuguese Study.

INTRODUCTION: Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. METHODS: This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30 months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). RESULTS: A total of 312 patients were included in the study, with 56.4% being male (median age of 30 years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30 months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. CONCLUSIONS: This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.

Piebaldism and neurofibromatosis: state of knowledge.

Despite progress in understanding the molecular basis, the diagnosis of neurofibromatosis 1 (NF 1) is based on clinical criteria, established by the National Institute of Health (NIH) Consensus Conference in 1987. The association of NF1 and piebaldism has been reported, but some authors disagree with this co-occurrence. In the light of present knowledge, we highlight that both entities might co-exist in the same patient.

Skin disorders in the neonatal intensive care unit of a central hospital.

Cutaneous abnormalities in the newborn are usually benign and transitory. However, they may sometimes be extremely distressing both for parents and the medical staff, presenting with significant morbidity and mortality. The aim of this study was to access the clinical features of different skin disorders in a series of newborns, at a level III neonatal intensive care unit (NICU) in the Northern Region of Portugal, and review some of the most impressive cases. Between January 1997 and December 2010, 27 patients were found to have an important cutaneous condition that required admission to the NICU. The most frequent presentations were vesicles and pustules (n=8; 29.6%), followed by erythroderma (n=7; 25.9%), atrophic (n=5; 18.5%) and vascular lesions (n=4; 14.8%). Four (14.8%) patients died in the neonatal period, and further 4 afterwards. Genetic studies, when available, revealed three chromosomal disorders and 6 gene mutations. Overall, skin disorders were not a leading cause of NICU admission (0.43%), but were associated with significant morbidity and mortality.

Recurrent Wells' syndrome associated with allergic asthma exacerbation.

Wells syndrome is an inflammatory eosinophilic dermatosis of unknown pathogenesis characterized by clinical polymorphism, a suggestive but nonspecific histopathologic traits, usually with a recurrent course and inconstant response to therapy. It seems to be an unspecific hypersensitivity reaction in response to various exogenous and endogenous stimuli, such as insect bites, infections, drug eruption or underlying internal disorders. We present a patient with allergic asthma and atopic dermatitis in whom a skin eruption developed in the sequence of allergic asthma exacerbation, which was clinically and histologically consistent with the diagnosis of eosinophilic cellulitis. The authors discuss the probability of a common pathogenesis and the role of IL-5. To our best knowledge this is the first pediatric case where this association is reported.

Erythema multiforme-like lesions revealing allergic contact dermatitis to exotic woods.

We report a 45-year old man who developed maculopapular exanthema on the inferior cervical folder, axillae and umbilicus, as well as erythema multiforme-like lesions on the wrists after the introduction in his work of pao ferro (Machaerium scleroxylon). Patch tests were positive to pao ferro and ebony. This case highlights the importance of patch tests for the confirmation of the culprit agent in occupational dermatoses and also to identify other occupational allergens that the patient should avoid. Tropical woods contain quinones that could explain the possible cross-reactions between woods belonging to different families.

Adverse Cutaneous Drug Reactions in Children: A Retrospective Study in a Tertiary Hospital.

Adverse reactions to drugs are a major concern in health, and children seem to be particularly vulnerable to these reactions. Cutaneous reactions account for 35% of the drug-related adverse effects in children. We conducted a retrospective study to characterize the pediatric population having a diagnosis of cutaneous adverse drug reactions (CADRs) in children admitted in a tertiary hospital during 6 years. (SKINmed. 2022;20:126-129).

Clinicopathological features of head and neck cutaneous basal cell carcinoma observed at the Centro Hospitalar de Trás-os-Montes e Alto Douro ENT Department.

Background: Cutaneous basal cell carcinoma (cBCC) incidence has been increasing, but there are no available data on its epidemiological, clinical, and pathological patterns in Northeast Portugal. cBCC is mainly located in the head and neck, where the ear, neck, and throat (ENT) surgeon may have a major role. We aimed to verify the clinicopathological characteristics of basal cell carcinomas diagnosed in an ENT department. Methods: We performed a retrospective clinicopathological evaluation of the head and neck cBCC cases followed up at the Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD) ENT Department between January 2007 and April 2021. Results: One hundred seventy-four patients with 293 cBCCs were included in this retrospective study. We observed that about one-third of the patients had multiple cBCCs (30.5%) and an infiltrative-type growth pattern (39.3%), both features considered as patterns that are more aggressive. Infiltrative-type growth pattern cBCCs were significantly larger when compared with the indolent-type growth pattern (16.2 mm vs 10.8 mm). Conclusions: To the best of our knowledge, this is the first study about cBCC in a patient population followed up at an ENT hospital department. This study has shown that these patients had cBCCs with more aggressive features, making these tumors an important issue for the ENT surgeon.

Comparison of non-criteria antiphospholipid syndrome with definite antiphospholipid syndrome: A systematic review.

Objectives: Patients with laboratory or clinical manifestations suggestive of antiphospholipid syndrome (APS) but not fulfilling the classification criteria constitute a clinical challenge. This study aims to compare non-criteria APS (NC-APS) with definite APS in terms of clinical manifestations, therapies, and outcomes. Methods: A systematic review of observational studies comparing definite and NC-APS was performed searching four electronic databases. Data on clinical manifestations, therapies and clinical outcomes was extracted. Results: Sixteen studies, assessing a total of 3,798 participants, were included. Seven out of 10 studies found no significant difference in the prevalence of arterial or venous thrombosis between definite and NC-APS, with two studies on seronegative APS also finding no difference in thrombosis recurrence. Seven out of 12 studies found no significant difference in the prevalence of obstetric manifestations between groups, with the remaining exhibiting conflicting results. In 9 studies comparing treatment frequency in obstetric patients, all but one described similar treatment frequency, with the percentage of NC-APS treated during pregnancy ranging from 26% to 100%. In 10 studies comparing pregnancy outcomes of NC-APS versus definite APS, 7 found similar successful pregnancies/live births. Additionally, 5 studies described improvement of live births in both groups with treatment, with three signalling aspirin monotherapy as efficacious as combination therapy in NC-APS. Conclusion: This review hints at an absence of marked differences in most evaluated parameters between definite and NC-APS, emphasizing the value of a more active follow-up of these patients. The low-quality available evidence highlights the need for well-defined NC-APS populations in future studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42020210674.

Erythropoietic protoporphyria: a family study and report of a novel mutation in the FECH gene.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis mostly caused by a deficient activity of the enzyme ferrochelatase (FECH), and consequent accumulation of protoporphyrin (PP) in various tissues. Clinical manifestations include a childhood onset, cutaneous photosensitivity and, sometimes, hepatobiliary disease. We report a 16-year-old male with EPP characterized by acute episodes of painful photosensitivity since early infancy, permanent changes in the photoexposed skin, microcytic anemia, thrombocytopenia, and mild hepatic dysfunction. His 18-year-old sister presented less acute symptoms with no chronic changes. Lesional biopsy disclosed perivascular deposition of PAS positive hyaline material. Rimington-Cripps test was positive and PP erythrocyte levels were >9,000 µg/L (N<1,600), but normal in their parents and younger brother. Genetic studies in both patients and their mother revealed heterozygosity for a novel mutation (c.1052delA) in FECH gene of both children, and heterozygosity for the hypomorphic allele IVS3-48T>C in all of them. This confirms the "pseudodominant" inheritance pattern usually observed, explained by the combined presence of a disabling FECH mutation and a common intronic polymorphism affecting the counterpart allele (IVS3-48T>C). Phenotypic heterogeneity for this genotype explains the divergent clinical presentation. This is the first description of a Portuguese family with EPP characterized at the molecular level.

Acute hemorrhagic edema of childhood after H1N1 immunization.

Acute hemorrhagic edema (AHE) is an uncommon self-limited disorder affecting young children triggered by infection, drugs, or immunization. A 2-year-old boy was observed due to sudden onset of painful and edematous purpuric papular and plaque lesions of the face and upper extremities that started 2 weeks after H1N1 immunization. The patient also developed exuberant edema on the face and dorsum of the hands. Complete blood count, biochemistry, and urinalysis results were normal. Histopathological examination revealed perivascular and periadnexial lymphocytic infiltrate with neutrophils and eosinophils, and leukocytoclastic vasculitis. Blood PCR technique was negative to several viruses, namely adenovirus, cytomegalovirus, Epstein Barr, enterovirus, HHV6, parvovirus B19, and H1N1. Symptomatic treatment and parents reassurance was promptly provided. However, new lesions continued to develop and in this setting systemic corticosteroid was prescribed. Complete clinical resolution was achieved within 2 weeks and no relapse was observed. The temporal relationship with H1N1 immunization, absence of previous drug intake, as well as exclusion of viral infections led the authors to propose that H1N1 vaccine was the predisposing factor in AHE development in our patient. To our best knowledge, this is the first reported association between AHE and H1N1 immunization.

Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leukocytoclastic vasculitis induced by propylthiouracil confirmed by positive patch test: a case report and review of the literature.

A 43-year-old female with antiphospholipid syndrome and Graves' disease developed a cutaneous leukocytoclastic vasculitis associated with antineutrophil cytoplasmic antibody (ANCA) against myeloperoxidase (MPO-ANCA) and proteinase-3 (PR3-ANCA), whilst treated with propylthiouracil (PTU). The skin lesions were progressively resolved after withdrawal of PTU and treatment with oral steroids. Patch testing with PTU at 1%, 5%, and 10% in petrolatum was positive at 48 h. Despite positive ANCA titers after 1 year of follow-up, the patient maintains complete clinical remission. PTU is a common antithyroid drug, which has been known to induce ANCA-positive vasculitis. Although most patients with this rare side effect have a good outcome, some fatal cases have been reported. Therefore, patients treated with PTU should be carefully followed and monitored, not only for their thyroid state but also for early detection of potential serious complications of this drug. Early diagnosis and prompt cessation of PTU therapy are essential to improve the outcome. Also key aspects of PTU-induced ANCA-positive vasculitis are reviewed.

Vascular Ehlers-Danlos syndrome: a case with fatal outcome.

A 13-year-old boy, born prematurely and hypotonic, from non-consanguineous healthy parents, was referred to our department because of easy bruising. A slightly extensible, thin and translucent skin, associated with dysmorphic facies, acrogeria, multiple ecchymoses, hypermobility of the small joints, dorsal kyphosis, genu valgum, flat feet, elongated upper limbs, and low muscle tone were all evident. A history of learning disability and bilateral inguinal hernia was present. Blood and imaging studies were unremarkable. A skin biopsy disclosed an unremarkable dermis; electron microscopy showed abnormalities in the diameter, contour, and shape of collagen fibrils/fibers. Genetic analysis revealed heterozygosity for a novel mutation in COL3A1 gene (c.3527G>A), confirming the diagnosis of vascular Ehlers-Danlos syndrome (VEDS). The patient died at 15 years of age because of aortic dissection. Vascular Ehlers-Danlos syndrome is a rare, life-threatening, autosomal dominant variant of EDS, resulting from mutations in COL3A1 gene. Affected individuals are prone to serious and potentially fatal complications, especially vascular, intestinal, and uterine ruptures. Delay in diagnosis is common, even when the clinical presentation is typical. Therefore, dermatologists should be familiar with VEDS features because the skin findings may be the first signs. Early diagnosis will improve management of visceral complications and allow early genetic counseling.

Diffuse Large B-Cell Lymphoma in the Setting of Chronic Lymphocytic Leukemia.

A 77-year-old man was referred to our department with a 6-month history of a painless, rapidly enlarging tumor on the left leg. Fourteen years ago, he was diagnosed with chronic lymphocytic leukemia (CLL), and he had presented with lymphocytosis and multiple lymphadenopathies (Rai stage II). Both bone marrow aspiration and peripheral blood immunophenotyping identified a monoclonal B-cell population expressing surface CD5, CD20, CD23, CD43, and IgG kappa. At that time, he underwent eight courses of treatment with oral fludarabine, followed by complete remission, and he had been clinically stable ever since (Rai stage 0).

Langerhans Cell Histiocytosis-A Benign Presentation Heralding a Serious Disease.

A 3-year old White boy was referred to our dermatology department with a papular disseminated eruption, evolving for 7 months. Several topical antibiotics and corticosteroids were used without improvement. The dermatosis was locally asymptomatic, and systemic symptoms were absent. Examination revealed multiple, skin-colored to pinkish monomorphic papules with a generalized distribution involving the face, trunk, and limbs (Figure 1). The lesions spared the scalp, palms, and soles. Cervical, axillary, and inguinal lymphatic nodes were not palpable. Cutaneous biopsy of one of the abdominal lesions revealed an unremarkable epidermis but a reticular dermis with clusters of histiocytic, lymphocytic, and rare eosinophil cells. In the immunohistochemical study, expression of CD1a was observed in the histiocytic cells and S100 in the antigen-presenting cells of the dermal infiltrate (Figures 2 and 3). Taking into account the clinical presentation and the histopathologic result, a diagnosis of Langerhans cell histiocytosis (LCH) was established.