Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency.

PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children. METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method. RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.

Ecthyma gangrenosum in pediatric patients: 10-year experience at the National Institute of Pediatrics.

BACKGROUND: Ecthyma gangrenosum (EG) usually results from the hematogenous seeding of the skin in the setting of bacteremia, mostly by Pseudomonas aeruginosa, especially in immunocompromised patients. It presents as erythematous-violaceous macules, or plaques with surrounding erythema before rapidly progressing to bullae and necrotic-ulcerative eschars. METHODS: We performed a retrospective chart review of EG patients diagnosed at the National Institute of Pediatrics. Data included demographics, underlying disease, cutaneous lesions, location, evolution, microbiologic, histopathologic findings, and treatment. Data were analyzed by descriptive statistics; Mann-Whitney U test and Fisher's exact test were used to evaluate differences between groups. RESULTS: Seventeen patients with a mean age of 12.5 (6-16) years were included. The most common underlying disease was acute lymphoblastic leukemia (59%), three patients were not immunocompromised (17%). A total of 18 episodes of EG were recorded, 10 (55%) were disseminated at presentation. Systemic manifestations included fever (100%), pain (88.9%), asthenia and adynamia (22.2%). P. aeruginosa was isolated in 10 (55%) cases, followed by Staphylococcus aureus in four. Three patients had sepsis at onset (17%). A comparison between localized versus disseminated, pseudomonal versus nonpseudomonal, and bacteremic versus nonbacteremic EG was performed with no statistical difference between any of the groups, except for longer treatment time for pseudomonal EG, and longer hospitalization days for both pseudomonal EG and bacteremia. CONCLUSIONS: Fever and pain in the setting of rapidly evolving necrotic lesions should prompt the clinical suspicion of EG and the installment of empiric treatment pending culture results.

Pachydermodactyly: Soft Tissue Enlargement of the Fingers in a Teenager.

Pachydermodactyly (PDD) is an uncommon and benign digital fibromatosis of unknown etiology. It is characterized by a fusiform swelling of the medial and lateral sides of the fingers, with unspecific histopathological features of an increased number of fibroblasts, collagen, and mucin deposit in the dermis. Due to its rarity, PDD could be misdiagnosed as rheumatic arthropathies, which could lead to unnecessary immunosuppressant treatments. Here, we report the case of a 16-year-old boy who presented progressive and asymptomatic soft tissue enlargement of multiple fingers in both hands. The histopathological study and X-ray findings correlated with PDD diagnosis. Intralesional corticoid treatment was indicated with a mild improvement.

Epidermolysis Bullosa Acquisita: A Rare Autoimmune Blistering Disease in Children.

A 7-year-old girl presented with a 2-year history of recurrent blisters on the skin and oral mucosa. The patient was otherwise healthy, and her family history was unremarkable for any dermatologic or other medical disease. Examination revealed multiple tense vesicles, milia, and atrophic scars present over the extensor surface of the extremities and erosions on the oral mucosa (Figure 1). A skin biopsy established a pauci-inflammatory subepidermal blister (Figure 2a). Direct immunofluorescence (DIF) evidenced the linear deposition of immunoglobulin G (IgG), immunoglobulin M (IgM), and κ and λ chains at the dermal-epithelial junction (DEJ). Indirect immunofluorescence (IIF), using the salt-split technique, established anti-epithelial antibodies on the dermal side (Figure 2b). An enzyme-linked immunosorbent assay (ELISA) was positive for Collagen Type VII (COL7) antibodies. A diagnosis of epidermolysis bullosa acquisita (EBA) was made, and treatment with azathioprine and deflazacort was administered for 8 months with progressive lessening of her symptomatology and complete clinical response at 2-year follow-up. (SKINmed. 2022;20:460-462).

Morphea mimicking facial capillary malformations: Two new cases and review of the literature.

Morphea and facial capillary malformations (port-wine stains) are distinct conditions that can affect the pediatric population. Early localized morphea mimicking a capillary malformation is an uncommon clinical presentation. We present two new cases of girls, aged 2 and 3 years, who presented with erythematous patches, initially diagnosed as capillary malformations, which were later diagnosed as morphea. We also performed a literature review, yielding 12 additional cases that underscore that the unusual presentation of morphea may delay correct diagnosis. Although early management of morphea reduces long-term sequelae, it is important to delay laser treatment for selected acquired vascular malformations, until the diagnosis of morphea is excluded.

Usefulness of Trichoscopy over Hair Light Microscopy in Menkes Disease.

Menkes disease (MD) is a rare X-linked recessive neurodegenerative disorder caused by mutations in the ATP7A gene, with a high mortality rate within the first 3 years of life. It typically affects males and is characterized by impaired copper distribution and malfunction of several copper-dependent enzymes. Patients develop progressive muscle hypotonia associated with neurological damage and hair shaft dysplasia - particularly pili torti. Pili torti is usually very subtle in the first 3 months of life and gradually increases during the first year. Light microscopy examination in search for pili torti requires the observation of more than 50 hair shafts. In contrast, trichoscopy with a hand-held dermatoscope allows to easily identify the hair shaft defect. We report a case of a Hispanic male infant with MD in whom we show that trichoscopy is superior to hair light microscopy in revealing pili torti.

Bronchiolitis Obliterans With Anti-Epiplakin Antibodies in a Boy With Paraneoplastic Pemphigus.

Paraneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by a recalcitrant and severe mucositis, and polymorphic cutaneous lesions, associated with benign and malignant neoplasms. Paraneoplastic pemphigus is caused by production of autoantibodies against various epidermal proteins involved in cell adhesion. Bronchiolitis obliterans (BO) is one of the leading causes of mortality in these patients. Recent advances have associated the presence of anti-epiplakin antibodies with the development of BO in adult patients. Here we describe the first pediatric patient in whom the association of anti-epiplakin antibodies and BO have been reported so far.

Kawasaki disease mimickers.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects patients younger than 5 years. In the absence of an available, affordable diagnostic test, detailed clinical history and physical examination are still fundamental to make a diagnosis. METHODS: We present five representative cases with KD-like presentations: systemic onset juvenile idiopathic arthritis, mycoplasma-induced rash and mucositis, staphylococcal scalded skin syndrome, BCGosis, and the recently described multisystemic inflammatory syndrome in children (MIS-C) associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus. RESULTS: Rash, fever, and laboratory markers of inflammation can be present in several childhood diseases that may mimic KD. CONCLUSION: The term 'Kawasaki syndrome' instead of 'Kawasaki disease' may be more appropriate. Physicians should consider an alternative diagnosis that may mimic KD, particularly considering MIS-C during the present pandemic, as an aggressive diagnostic and therapeutic approach is needed.

Clinical, trichoscopy, and light microscopic findings in hypohidrotic ectodermal dysplasia: Report of 21 patients and a review of the literature.

INTRODUCTION: Hypohidrotic ectodermal dysplasia (HED) is a genetic condition typified by alterations in skin structures including sweat glands, hair, nails, and teeth. Hair findings in HED have been poorly characterized in larger series. OBJECTIVE: To characterize scalp and hair findings of patients with HED clinically and with trichoscopy and light microscopy. METHODS: A cross-sectional study in 21 pediatric HED patients was performed using available clinical and scalp dermatoscopic images, as well as pulled-hair samples for clinical evaluation, trichoscopic, and light microscopic analyses. RESULTS: Seventeen out of 21 patients (81%) were men. Twenty patients had straight hair. Sixteen patients had decreased hair density, 6 of whom had hair loss mainly in the temporal and occipital regions. Fourteen patients had hair whorls. On trichoscopy, we observed: single-hair follicular units (n = 19, 90%), scalp hyperpigmentation (n = 13, 62%), variable diameter of the hair shafts (n = 12, 57%), perifollicular scales (n = 8, 38%), scalp erythema (n = 8, 38%), and short curly pigtail hairs (n = 6, 29%). On light microscopy, findings included: hair shafts with irregular diameter (n = 7, 33%), heterogeneous hair color (n = 6, 29%), trichoptilosis (n = 2, 10%), and pili torti (n = 1, 5%). CONCLUSIONS: In this series, hair findings in HED were similar to those described in previous studies. However, we describe two new clinical and two trichoscopic findings: decreased hair density mainly in the temporal and occipital regions, oblique upwards occipital hair follicles orientation, angled hairs, and short curly pigtail hairs. These heterogeneous findings may reflect the multiple factors and signaling pathways that can be affected in these syndromes.

Early clinical, histological, and immunohistochemical findings in suspected acute graft-versus-host disease and their association with patient outcomes.

BACKGROUND/OBJECTIVES: Acute graft-versus-host disease (aGVHD) is a serious condition after allogeneic hematopoietic stem cell transplantation (HSCT), frequently involving skin, gut, and liver. It can be difficult to diagnose early, yet this is vital for adequate management. We sought to identify initial clinical and histopathological features in children with suspected GVHD and the association with clinical course and outcomes. METHODS: Retrospective study of patients with skin biopsies for suspected aGVHD from 2006 to 2016. We collected demographic and clinical information, histologic, and immunohistochemical (IHC) findings, and outcomes during follow-up. Bivariate and multivariate analyses were done to identify risk factors associated with remission, development of severe/life-threatening aGVHD, and mortality. RESULTS: We included 42 patients, 15 females. Skin manifestations occurred 51 days (median) after HSCT. On biopsy, 76.2% had mild (stage 1-2) skin aGVHD; during the course of the disease, severity and systemic involvement increased to global grade III/IV in 66.6%. All patients received treatment; 15 are in remission from aGVHD and 23 have died. Histologic features were diagnostic in 83.3%. On bivariate and multivariate analysis, we identified initial clinical and histologic findings that were associated with the measured outcomes: odds of remission from aGVHD were increased when focal vacuolar changes were found on skin biopsy (OR 6.028; 95%CI:1.253-28.992) but decreased by initial hepatic aGVHD (OR 0.112; 95%CI: 0.017-0.748); severe/life-threatening aGVHD was associated with initial gastrointestinal aGVHD (OR 6.054; 95%CI:1.257-29.159); and odds of mortality were decreased with male donor (OR 0.056; 95%CI:0.004-0.804), nulliparous female donor (OR 0.076; 95%CI:0.009-0.669), and focal vacuolar changes on skin biopsy (OR 0.113; 95%CI:0.017-0.770). CONCLUSIONS: We found novel indicators predictive of remission, severity, and mortality in children with aGVHD. Further studies of this condition in children are needed.

Are apoptosis-determining techniques useful to establish an early diagnosis of acute graft-vs-host disease in pediatric patients under treatment with multiple drugs?

BACKGROUND: There are no pathognomonic histopathological features to distinguish acute graft-vs-host disease (aGVHD) from skin drug reactions (SDRs) in pediatric patients with multiple drug regimens that have received blood transfusions and/or transplants. We aimed to determine if the addition of apoptosis markers is helpful to distinguish aGVHD from SDRs in these patients. METHODS: Skin biopsy specimens from patients with a clinical diagnosis of aGVHD or SDRs were evaluated for the presence of apoptotic bodies, satellitosis, interface damage, vasculitis, and inflammatory infiltrate on H&E stain. Information was completed with apoptotic markers (transferase-mediated dUTP nick end-labeling [TUNEL], bcl-2, and caspase-3). RESULTS: The skin biopsy specimens of 32 patients with aGVHD and 11 with SDRs were included for study. Only the number of apoptotic keratinocytes per 10 high-power fields (hpf) showed a significant difference between both groups (P = 0.02); the presence of ≥4 apoptotic keratinocytes per 10 hpf was identified as the optimal cut-off point to discriminate aGVHD from SDRs. No SDRs cases had follicular apoptotic cells. TUNEL, bcl-2, and caspase-3 determination showed no difference between both groups. CONCLUSIONS: The presence of ≥4 apoptotic keratinocytes per 10 hpf (in aGVHD) and the absence of follicular apoptotic cells (in SDRs) might be a useful marker to distinguish between them.

Hemangioma infantil: actualización del tratamiento tópico y sistémico / Infantile hemangioma: an update in the topical and systemic treatments

Resumen Los hemagiomas infantiles (HI) son los tumores de tejidos blandos más frecuentes de la infancia. Se caracterizan por un crecimiento significativo durante los primeros meses de vida, seguido de una involución lenta y espontánea a lo largo de un periodo que puede durar algunos años. Usualmente, la regresión de la mayor parte del tumor termina a los 4 años de edad. Sin embargo, algunos de los HI desarrollan complicaciones, lo que resulta en alteraciones funcionales, dolor y desfiguramiento. La decisión de administrar tratamiento a un paciente con HI y elegir la mejor opción terapéutica para ese paciente (tratamiento tópico o sistémico) debe ser individualizada, dependiendo de varios factores: el tamaño de la lesión, la localización, la presencia de complicaciones como ulceración, el riesgo de cicatrización o desfiguramiento, la edad del paciente, la tasa de crecimiento o de involución al momento del diagnóstico, los riesgos y beneficios de administrar el tratamiento, la disponibilidad del medicamento, los costos y la experiencia del médico tratante.

Abstract Infantile hemagiomas (IH) are the most common soft tissue tumors in infancy. They are characterized by significant growth during the first months of life, followed by slow spontaneous involution over the ensuring years. The process of involution takes several years, but usually the regression of most of the tumors ends at 4 years of age. Unfortunately, some of the IH develop complications, resulting in functional impairment, pain and disfigurement. The decision to start treatment and the choice of the best therapeutic option (topic or systemic) should be individualized depending on several factors: the size of the lesion, the location, the presence of complications such as ulceration, the risk of scarring or disfigurement, the age of the patient, the rate of growth or regression at the time of diagnosis, the risks and benefits of the treatment, the availability of the medication, the costs, and the experience of the attending physician.

Infantile hemangioma: an update in the topical and systemic treatments.

Infantile hemagiomas (IH) are the most common soft tissue tumors in infancy. They are characterized by significant growth during the first months of life, followed by slow spontaneous involution over the ensuring years. The process of involution takes several years, but usually the regression of most of the tumors ends at 4 years of age. Unfortunately, some of the IH develop complications, resulting in functional impairment, pain and disfigurement. The decision to start treatment and the choice of the best therapeutic option (topic or systemic) should be individualized depending on several factors: the size of the lesion, the location, the presence of complications such as ulceration, the risk of scarring or disfigurement, the age of the patient, the rate of growth or regression at the time of diagnosis, the risks and benefits of the treatment, the availability of the medication, the costs, and the experience of the attending physician.

Los hemagiomas infantiles (HI) son los tumores de tejidos blandos más frecuentes de la infancia. Se caracterizan por un crecimiento significativo durante los primeros meses de vida, seguido de una involución lenta y espontánea a lo largo de un periodo que puede durar algunos años. Usualmente, la regresión de la mayor parte del tumor termina a los 4 años de edad. Sin embargo, algunos de los HI desarrollan complicaciones, lo que resulta en alteraciones funcionales, dolor y desfiguramiento. La decisión de administrar tratamiento a un paciente con HI y elegir la mejor opción terapéutica para ese paciente (tratamiento tópico o sistémico) debe ser individualizada, dependiendo de varios factores: el tamaño de la lesión, la localización, la presencia de complicaciones como ulceración, el riesgo de cicatrización o desfiguramiento, la edad del paciente, la tasa de crecimiento o de involución al momento del diagnóstico, los riesgos y beneficios de administrar el tratamiento, la disponibilidad del medicamento, los costos y la experiencia del médico tratante.

Pulmonary nodules and nodular scleritis in a teenager with superficial granulomatous pyoderma gangrenosum.

Superficial granulomatous pyoderma gangrenosum, a rare variant of pyoderma gangrenosum, has been considered to be the most benign form of the disease. We present the case of a 15-year-old boy with pulmonary involvement and nodular scleritis associated with this unusual type of pyoderma gangrenosum and discuss its differential diagnosis.

Sporadic progressive mucinous histiocytosis in a Mexican patient.

A 33 year-old woman presented with numerous 3- to 5-mm red-brown and yellow-brown dome-shaped nodules, primarily located on the scalp, dorsal aspects of the forearms, and lower extremities (Figure 1 and Figure 2). Her lesions started to appear 5 years prior to her consultation with increasing number and without spontaneous regression. Findings from a previous biopsy revealed epithelioid dermatofibroma. The remainder of the physical examination was unremarkable. There were no familial cases of this condition (both the mother and two older sisters were examined).

Hydroa vacciniforme-like lymphoma: a chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma.

Hydroa vacciniforme-like lymphoma (HVLL) is an Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder of childhood that occurs mainly in Central and South America and Asia. We present the clinicopathological features of 20 Mexican children with HVLL with a median age of 8 years at diagnosis (range, 1-15). All patients presented with skin lesions involving sun-exposed areas, but not exclusively. Fever, lymphadenopathy, and hepatosplenomegaly were often observed. Most patients were treated with immunomodulators and/or immunosuppressive agents, resulting in temporary remission. For 13 patients follow-up was available for a median of 3 years (range, 1 month-13 years). Three patients with long follow-up (9-13 years) are alive with disease. Four patients died, 2 after developing systemic lymphoma. Histologically, the skin showed a predominantly angiocentric and periadnexal Epstein-Barr early RNA+ lymphoid infiltrate with variable atypia and subcutaneous involvement. Fifteen patients showed a T-cell phenotype (12, αß; 2, γδ; 1, silent phenotype) and monoclonal T-cell receptor-γ rearrangements, whereas 6 exhibited a natural killer (NK)-cell phenotype. Four patients had hypersensitivity to mosquito bites. One patient showed both phenotypes. HVLL is an EBV-associated lymphoproliferative disorder of αß-, γδ-, or NK-cell phenotype with a broad clinical spectrum, usually prolonged clinical course, and risk for progression to systemic disease.

Dermoid cysts: a report of 75 pediatric patients.

Dermoid cysts (DCs) are benign cutaneous tumors that tend to persist and grow. The aim of this study was to examine the clinicopathologic features of congenital DCs. We present a case series of 75 children with a clinicopathologic diagnosis of DC. Seventy-two cysts were located on the head, one on the neck, and two on the trunk. Six cysts were located along the midline. Eight patients had symptoms other than changes in cyst size. Imaging studies were performed on 15 patients. Surgical excision was the primary treatment in all 75 cases. Neurosurgery and ophthalmology services were involved in the care of some patients. Histopathologic studies reported a foreign body giant cell reaction in 17 of the cysts. No recurrence was documented. DCs can remain stable for years, but they can become symptomatic as a result of enlargement and rupture or, more rarely, as a result of extension into surrounding tissues. Physicians should be aware that certain locations have a higher risk of DC extension, and adequate diagnostic investigations should be performed before their complete resection.