Severe eczema in Wiskott-Aldrich syndrome-related disorder successfully treated with dupilumab.

Treatment of severe eczema in patients with primary immunodeficiencies can be particularly challenging as there are no guidelines with regards to these conditions. Dupilumab is an interleukin (IL)-4Rα antagonist that inhibits both IL-4 and IL-13 and is approved for the treatment of atopic dermatitis in pediatric patients. In this report, we describe a patient with a case of severe eczema in the context of Wiskott-Aldrich syndrome-related disorder, who was successfully treated with dupilumab.

Membranous nephropathy in a female patient with X-linked thrombocytopenia.

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia and eczema and is caused by a mutation in the WAS gene. WAS has heterogeneous clinical manifestations, and its clinically milder form is called X-linked thrombocytopenia (XLT). Patients with WAS/XLT sometimes have kidney complications, the most common of which is immunoglobulin (Ig)A nephropathy associated with aberrant glycosylation of IgA. CASE DIAGNOSIS/TREATMENT: The patient was a 6-year-old girl who was diagnosed with female XLT at the age of 4 years; she presented with microscopic hematuria and proteinuria at a school urinalysis. Her father had thrombocytopenia and IgA nephropathy while in his 20 s. The patient and her father had the same WAS gene mutations. A kidney biopsy was performed, and no abnormal findings were observed by light microscopy. Immunofluorescence analysis revealed a granular pattern of IgG staining along the capillary wall. Electron microscopy revealed small electron-dense deposits in subepithelial lesions. Consequently, we diagnosed her with membranous nephropathy (MN). Tissue PLA2R and THSD7A were negative, and she was judged unlikely to have secondary MN on the basis of blood test findings and IgG staining. We started the administration of angiotensin-converting enzyme inhibitors, and her proteinuria gradually decreased. CONCLUSION: To our knowledge, this is the first report of MN in a female WAS/XLT patient. WAS protein expression defects affect all immune system cells; however, the mechanisms underlying the occurrence of autoimmunity are not completely understood. In WAS/XLT patients, MN may develop as a result of increased autoantibody production, similar to other types of immunodeficiency.

CMV Retinitis in Wiskott Aldrich Syndrome.

PURPOSE: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may suffer from cytomegalovirus retinitis (CMVR) which can cause vision loss. This study is to report the progression and prognosis of patients with WAS and CMVR. METHODS: A retrospective case series of ten patients with WAS and CMVR before and after HSCT who were referred to the Ophthalmology Department of Xinhua Hospital from June 2018 to February 2021. Progression and prognosis were recorded. RESULTS: Five patients were diagnosed with CMVR before receiving HSCT at a median age of 10.5 months (range: 4-23 months). Eight patients developed CMVR post-transplantation with a median interval from HSCT of 3.5 months (range: 1-9 months). CONCLUSION: Regular fundus examinations and prompt treatments in patients with WAS are therefore crucial before they receiving HSCT or approximately 3.5 months after HSCT until complete reconstitution of immune function.

Atypical Wiskott-Aldrich syndrome without thrombocytopenia partially responding to omalizumab therapy.

Primary immunodeficiencies with eczema can be easily misdiagnosed as atopic eczema, and thus require a high degree of awareness for diagnosis. Wiskott-Aldrich syndrome (WAS) is a rare disease and the fact that WAS without microthrombocytopenia has not been reported to date makes this case more interesting. As the patient's predominant problem was eczema and he had high circulating IgE antibodies in his serum, omalizumab was chosen as an appropriate steroid-sparing treatment option, as it has been shown to be effective in previous studies.

Acquired Thrombotic Thrombocytopenic Purpura in a 5-Year-old Child With Wiskott-Aldrich Syndrome.

Thrombocytopenia is often seen as a laboratory finding during childhood. A supposed idiopathic thrombocytopenic purpura patient who was later diagnosed as Wiskott-Aldrich syndrome (WAS) and developed acquired thrombotic thrombocytopenic purpura (aTTP). Although autoimmune manifestations in WAS described, aTTP was reported just once. Five-year-old-boy was initially brought with cough, bloody stool (diarrhea), oral mucosal bleeding at 12th months of age. Following diagnosed with idiopathic thrombocytopenic purpura and receiving intravenous immunoglobulin, platelet count raised from 20,000 to 50,000/µL. One year after WAS diagnosis by mutation analysis, he presented with complaints of resistant fever, epistaxis, and melena. Hemoglobin decreased from 10 to 5.9 g/dL. Schistocytes in peripheral blood smear and high anti-ADAMTS-13 antibody level indicated development of aTTP.

A case of early recurrent immunoglobulin A nephropathy and T-cell-mediated rejection in a transplant patient with Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is an X-chromosome recessive immunodeficiency disease characterized by the triad of thrombocytopenia, eczema, and susceptibility to infection owing to WAS protein gene abnormalities. Kidney transplantation is rarely offered to WAS patients with end-stage renal disease because of concerns that thrombocytopenia and immune disorders may affect the clinical outcome. Here, we report the case of a 20-year-old kidney transplant patient who developed end-stage renal disease owing to immunoglobulin (Ig)A nephropathy caused by WAS. Despite recurrent IgA nephropathy and T-cell-mediated rejection 7 months after transplantation, two rounds of steroid pulse therapy attenuated his renal function and urinary abnormality. His serum creatinine level was maintained at approximately 1.5 mg/dL 1 year after transplantation. No other WAS-related complications were observed throughout the clinical course. Although WAS can cause poor prognosis in kidney transplant patients, careful follow-up may allow kidney transplantation to be performed.

Wiskott Aldrich syndrome: healthcare utilizations and disparities in transplant care.

Wiskott Aldrich syndrome (WAS) is a rare disease and hematopoietic stem cell transplant (HCT) is considered the treatment modality of choice for WAS. We conducted a cross-sectional analysis on the KIDS' pediatric inpatient database and compared hospitalization rates, complications and healthcare utilizations in the transplant and non-transplant arms. Of the 383 pediatric admissions with diagnosis of WAS between 2006-2012, 114 underwent transplant and 269 did not. The non-transplant arm included older children, female patients and more African Americans. Death rates, income and payer source were similar in both arms, however the total charge for each admission was higher in the transplant arm. Emergency room visits were similar but non-elective admissions were more in the non-transplant arm. Length of stay was prolonged in the transplant arm. When comparing morbidities, lymphomas, ulcerative colitis and autoimmune complications of WAS were seen only in the non-transplant arm. Our study shows that transplant is the largest contributor to healthcare utilization in WAS patients. We identified healthcare disparities based on race and socioeconomic status and found that this rare disease is being appropriately directed to centers with HCT expertise. We noted a change in practice moving away from splenectomy in WAS patients.

A Homozygous Mutation in 5' Untranslated Region of TNFRSF11A Leading to Molecular Diagnosis of Osteopetrosis Coinheritance With Wiskott-Aldrich Syndrome.

Wiskott-Aldrich syndrome (WAS) and osteopetrosis are 2 different, rare hereditary diseases. Here we report clinical and molecular genetics investigations on an infant patient with persistent thrombocytopenia and prolonged fever. He was clinical diagnosed as osteopetrosis according to clinical presentation, radiologic skeletal features, and bone biopsy results. Gene sequencing demonstrated a de novo homozygous mutation in 5'-untranslated region of TNFRSF11A, c.-45A>G, which is relating to osteopetrosis. Meanwhile, a hemizygous transition mutation in WAS gene, c.400G>A diagnosed the infant with WAS. This is the first clinical report for the diagnosis of osteopetrosis coinheritance with WAS in a single patient.

A Case With Wiskott-Aldrich Syndrome and Ascending Aorta Aneurysm.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder that is characterized by a triad of microthrombocytopenia, severe immunodeficiency, and eczema. We report the case of a 7-year-old male patient with chronic thrombocytopenia that was diagnosed as WAS after dilatation of the ascending aorta was noticed. WAS is rare, and it is a disease that requires high suspicion for diagnosis. We recommend periodic echocardiography and magnetic resonance imaging examinations to evaluate aortic aneurysms in children with WAS and that surgical intervention should not be delayed when aneurysm is detected.

Efficacy of romiplostim in treatment of thrombocytopenia in children with Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a life-threatening primary immunodeficiency associated with bleeding of variable severity due to thrombocytopenia. Correction of the thrombocytopenia is of paramount importance for most WAS patients. We report a retrospective analysis of the safety and efficacy of romiplostim treatment in reducing thrombocytopenia and bleeding tendency in 67 children (median age 1·3 years) with genetically confirmed WAS, followed in eight months (range, 1-12 months). Complete or partial primary responses regarding platelet counts were observed in 22 (33%) and 18 (27%) subjects, respectively. Yet, even in the non-responder group, the risk of haemorrhagic events decreased significantly, to 21%, after the first month of treatment. The responses tended to be durable and stable over time, with no significant fluctuations in platelets counts. The results of this retrospective study of a large cohort of WAS patients demonstrates that romiplostim can be used to increase platelet counts and reduce the risks of life-threatening bleeding in WAS patients awaiting haematopoietic stem cell transplantation or forgoing the procedure for various reasons.

Clinical Features and Outcomes of 23 Patients with Wiskott-Aldrich Syndrome: A Single-Center Experience

Objective: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency characterized by microthrombocytopenia, eczema, and recurrent infections. We aimed to evaluate the clinical features and outcomes of a WAS cohort. Materials and Methods: We retrospectively evaluated the clinical courses, immunological features, treatments, and outcomes in a total of 23 WAS patients together with data related to 11 transplanted cases among them between 1982 and 2019. Results: Before admission, 11 patients (48%) were misdiagnosed with immune thrombocytopenia. WAS scores were mostly 4 or 5. Eleven patients were transplanted and they had an overall survival rate of 100% during a median follow-up period of 8.5 years (range: 8 months to 20 years). Five patients who were not transplanted died at a median of 7 years (range: 2-26 years). Nontransplanted patients had high morbidity due to organ damage, mostly caused by autoimmunity, bleeding, and infections. Two novel mutations were also defined. Conclusion: All male babies with microthrombocytopenia should be evaluated for WAS. Hematopoietic stem cell transplantation should be performed at the earliest age with the best possible donors.

Guillain-Barré Syndrome and Hydrocephalus in an infant with Wiskott-Aldrich Syndrome. / Síndrome de Guillain Barré e hidrocefalia en un lactante con Síndrome de Wiskott Aldrich.

INTRODUCTION: Guillain-Barre Syndrome (GBS) is rarely diagnosed in the first year of life. The association of GBS with Wiskott-Aldrich syndrome (WAS) is even less frequent and has been previously reported in only two children to our knowledge. Hydrocephalus is a known but rare complication of GBS. OBJECTIVE: To describe the case of an infant in which GBS, WAS and hydrocephalus appear clinically associated. CLINICAL CASE: A nine-months-old male infant with a history of WAS was admitted to our ICU with acute hypotonia and poor general condition. He developed flaccid paralysis, absent deep tendon reflexes, and respiratory failure. A lumbar puncture showed albuminocytologic dissociation. GBS was suspected and an electromyography was performed, showing a demyelinating polyneuropathy. He was successfully treated with intravenous immunoglobulins. During hospitalization, he presented intermittent bradycardia, so a brain CT scan was performed, showing acute hydrocephalus which was managed through an external ventricular drain achieving favorable response. In the long term, the patient underwent bone marrow transplant and had to be reoperated due to valve-related complications. However, his psychomotor development is normal, with no obvious neurological sequelae. CONCLUSION: We present the third case of GBS in a patient with WAS, which is the first infant younger than one year. Additionally, he presented acute hydrocephalus as a complication of GBS. We suggest considering these three comorbidities since their early diagnosis and prompt management allow bet ter neurological recovery and avoid potentially lethal complications.

[Aortic aneurysm in a patient with Wiskott-Aldrich syndrome]. / Aneurisma aórtico en un paciente con síndrome de Wiskott-Aldrich.

BACKGROUND: The Wiskott-Aldrich syndrome is a combined immunodeficiency associated with a syndrome linked to the X chromosome, which is characterized by eczema, recurrent infections, and thrombocytopenia. Other manifestations include autoimmune disorders such as hemolytic anemia or thrombocytopenic purpura mediated by the immune system, increased susceptibility to malignant tumors, including lymphoma or leukemia. CLINICAL CASE: A 7-year-old male patient with a diagnosis of Wiskott-Aldrich syndrome who was treated with intravenous gamma globulin, antimicrobial prophylaxis with trimethoprim/sulfamethoxazole, and fluconazole, as well as with prednisone and cyclosporine due to hemolytic anemia and uveitis. Suddenly, he presented a deviation of the left labial commissure, so he was hospitalized. The studies showed a giant aneurysm of the aorta root, ascending aorta, descending aorta, and right coronary aorta, with insidious cardiac symptoms; therefore, he was referred to the vascular surgery department. CONCLUSION: Vasculitis in Wiskott-Aldrich syndrome is rare and it is usually asymptomatic in early stages, so an annual cardiovascular evaluation should be performed in order to avoid the complications of an aneurysm, which can be deleterious in this type of immunodeficiency where the possibility of death from bleeding is high.

Antecedentes: El síndrome de Wiskott-Aldrich es una inmunodeficiencia combinada asociada al síndrome ligado al cromosoma X, que se caracteriza por eccema, infecciones de repetición y trombocitopenia. Otras manifestaciones son los trastornos autoinmunes como anemia hemolítica o púrpura trombocitopénica mediada por el sistema inmunológico y susceptibilidad incrementada a tumores malignos, como linfoma o leucemia. Caso clínico: Niño de siete años, con diagnóstico de síndrome de Wiskott-Aldrich, en quien se estableció tratamiento con gammaglobulina intravenosa, profilaxis antimicrobiana con trimetoprima-sulfametoxazol y fluconazol, así como prednisona y ciclosporina debido a anemia hemolítica y uveítis. De forma súbita presentó desviación de la comisura labial izquierda, por lo que fue hospitalizado. Los estudios indicaron aneurisma gigante de la raíz de la aorta, aorta ascendente, descendente y coronaria derecha, con sintomatología cardiaca insidiosa, por lo que fue referido al servicio de cirugía vascular. Conclusiones: La vasculitis en el síndrome de Wiskott Aldrich es poco común y suele ser asintomática en las fases iniciales, por ello debe realizarse evaluación cardiovascular anual para evitar complicaciones propias de un aneurisma, que pueden ser deletéreas en este tipo de inmunodeficiencia, en las cuales existe mayor riesgo de muerte por sangrado.

Use of Thromboelastography to Guide Platelet Infusion in a Patient with Wiskott-Aldrich Syndrome Undergoing Renal Transplant.

Wiskott-Aldrich syndrome is a rare primary immuno-deficiency disorder that is characterized by a triad of microthrombocytopenia, eczema, and recurrent infections. Progression to end-stage renal failure is common in survivors due to immunoglobulin A nephropathy. We describe the case of a 24-year-old male with Wiskott-Aldrich syndrome. The patient had previous hematopoietic stem cell transplant and was on hemodialysis due to end-stage renal failure. He subsequently underwent living-donor renal transplant from his mother as the donor. This is only the fifth case of renal transplant in a patient with Wiskott-Aldrich syndrome in the world. In all cases, the perioperative management of hemostatic function has been crucial. We used thromboelastography to guide our hemostatic decisions rather than platelet count, thus reducing exposure to unnecessary platelet transfusions and without increased bleeding risk. Our patient had an uneventful course after living-donor kidney transplant.

Síndrome de Guillain Barré e hidrocefalia en un lactante con Síndrome de Wiskott Aldrich / Guillain-Barré Syndrome and Hydrocephalus in an infant with Wiskott-Aldrich Syndrome

Resumen: Introducción: El Síndrome de Guillain-Barré (SGB) es raramente diagnosticado en lactantes menores de 1 año. Su asociación con el Síndrome de Wiskott Aldrich (SWA), es aún menos frecuente, y ha sido previa mente reportada sólo en dos pacientes a nuestro conocimiento. La hidrocefalia, es una complicación conocida, pero infrecuente del SGB. Objetivo: presentar el caso clínico de un lactante en el que se asocian las patologías de SGB, SWA e hidrocefalia. Caso Clínico: varon de 9 meses, portador de SWA hospitalizado en unidad de cuidados intensivos por hipotonía aguda y compromiso del estado gene ral. Evolucionó con parálisis fláccida, falla ventilatoria y arreflexia generalizada. Una punción lumbar mostró disociación albuminocitológica, y el estudio electrofisiológico mostró signos de polineuropatía desmielinizante severa. Se trató con inmunoglobulina, evolucionando en forma satisfactoria. Por bradicardia intermitente, se realizó tomografla axial computada cerebral (TAC), que mostró signos de una hidrocefalia aguda, manejada mediante válvula derivativa ventrículo peritoneal con favorable respuesta. En el largo plazo, se sometió a trasplante de médula ósea y debió ser reintervenido por complicaciones valvulares, sin embargo, su desarrollo psicomotor es normal sin secuelas neurológi cas evidentes hasta los 3 años. Conclusión: Presentamos el tercer caso de SGB en un paciente porta dor de SWA, destacando ser el primero de ellos en un lactante menor de 1 año. Adicionalmente, este niño presentó una hidrocefalia aguda como complicación del SGB. Consideramos relevante tener presente estas comorbilidades, debido a que su pronto diagnóstico y manejo oportuno, permiten una mejor recuperación neurológica y evitan complicaciones potencialmente letales.

Abstract: Introduction: Guillain-Barre Syndrome (GBS) is rarely diagnosed in the first year of life. The association of GBS with Wiskott-Aldrich syndrome (WAS) is even less frequent and has been previously reported in only two children to our knowledge. Hydrocephalus is a known but rare complication of GBS. Objective: To describe the case of an infant in which GBS, WAS and hydrocephalus appear clinically associated. Clinical Case: A nine-months-old male infant with a history of WAS was admitted to our ICU with acute hypotonia and poor general condition. He developed flaccid paralysis, absent deep tendon reflexes, and respiratory failure. A lumbar puncture showed albuminocytologic dissociation. GBS was suspected and an electromyography was performed, showing a demyelinating polyneuropathy. He was successfully treated with intravenous immunoglobulins. During hospitalization, he presented intermittent bradycardia, so a brain CT scan was performed, showing acute hydrocephalus which was managed through an external ventricular drain achieving favorable response. In the long term, the patient underwent bone marrow transplant and had to be reoperated due to valve-related complications. However, his psychomotor development is normal, with no obvious neurological sequelae. Conclusion: We present the third case of GBS in a patient with WAS, which is the first infant younger than one year. Additionally, he presented acute hydrocephalus as a complication of GBS. We suggest considering these three comorbidities since their early diagnosis and prompt management allow bet ter neurological recovery and avoid potentially lethal complications.

Eltrombopag Therapy in Children With Rare Disorders Associated With Thrombocytopenia.

Eltrombopag (ELT) is a thrombopoietin receptor activator that has shown efficacy in chronic immune thrombocytopenia. We report the outcome of ELT therapy in 4 children who were treated for rare hematologic disorders, including Pearson syndrome, DiGeorge syndrome, posttransplant allogeneic poor graft function (PGF), and Wiskott-Aldrich syndrome. The ELT tolerance in the analyzed group was good, with the exception of the child with Pearson syndrome, who experienced an exacerbation of cataracts and had to discontinue treatment. Thromboembolic events were observed in one child, who continued ELT therapy despite achieving normalized platelet counts. Independence from PLT transfusions was observed at the 4-week timepoint of therapy in patients with DiGeorge syndrome and PGF who responded to ELT. Discontinuation of therapy was successful in one child, who sustained the normal CBC values afterward. In 2 patients, an increase in neutrophil counts was observed during ELT therapy without additional intervention, and a positive correlation between neutrophil and platelet values during ELT therapy was observed in the child with PGF. ELT is effective in rare pediatric disorders, but response patterns are determined by the underlying disease. ELT shows promising results in patients, but constitutional hematopoiesis defects reduce the chances of a response.