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Background: Mutations in the Spleen tyrosine kinase (Syk) protein have significant implications for its function and response to treatments. Understanding these mutations and identifying new inhibitors can lead to more effective therapies for conditions like autosomal dominant hyper-IgE syndrome (AD-HIES) and related immunological disorders. Objective: To investigate the impact of mutations in the Syk protein on its function and response to reference treatments, and to explore new inhibitors tailored to the mutational profile of Syk. Methods: We collected and analyzed mutations affecting the Syk protein to assess their functional impact. We screened 94 deleterious mutations in the kinase domain using molecular docking techniques. A library of 997 compounds with potential inhibitory activity against Syk was filtered based on Lipinski and Veber rules and toxicity assessments. We evaluated the binding affinity of reference inhibitors and 14 eligible compounds against wild-type and mutant Syk proteins. Molecular dynamics simulations were conducted to evaluate the interaction of Syk protein complexes with the reference inhibitor and potential candidate inhibitors. Results: Among the analyzed mutations, 60.5% were identified as deleterious, underscoring their potential impact on cellular processes. Virtual screening identified three potential inhibitors (IDs: 118558008, 118558000, and 118558092) with greater therapeutic potential than reference treatments, meeting all criteria and exhibiting lower IC50 values. Ligand 1 (ID: 118558000) demonstrated the most stable binding, favorable compactness, and extensive interaction with solvents. A 3D pharmacophore model was constructed, identifying structural features common to these inhibitors. Conclusion: This study found that 60.5% of reported mutations affecting the Syk protein are deleterious. Virtual screening revealed three top potential inhibitors, with ligand 1 (ID: 118558000) showing the most stable binding and favorable interactions. These inhibitors hold promise for more effective therapies targeting Syk-mediated signaling pathways. The pharmacophore model provides valuable insights for developing targeted therapies for AD-HIES and related disorders, offering hope for patients suffering from Hyper IgE syndrome with allergic symptoms., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale: Hyperimmunoglobulin E syndrome (HIES) is a rare and complex immunoregulatory multisystem disorder characterized by recurrent eczema, skin and sinopulmonary infections, elevated serum immunoglobulin E levels, and eosinophilia. Onset is most likely in childhood, although infrequent adult cases have been reported. Early diagnosis is important. The use of the National Institutes of Health scoring system and the HIES signal transducer and activation of transcription 3 score can standardize the diagnosis of HIES., Patient Concerns: A 19-year-old woman presented with complaints of dry cough, pyrexia, dyspnea, and recurrent pneumonia. She had a history of milk allergy, recurrent eczema, suppurative otitis media, chalazia, and aphthous ulcers. Her parents had a consanguineous marriage., Diagnosis: HIES; severe pneumonia., Interventions: Voriconazole (200 mg iv 2 times/d) and flucytosine (1 g orally 4 times/d) for 3 weeks were administered, followed by oral administration of fluconazole for 3 weeks., Outcomes: The patient experienced near-complete remission of her respiratory symptoms. The patient was followed-up for one and a half years. During the follow-up, the patient presented again with cough and dyspnea and was again admitted to hospital. After being hospitalized for 3 weeks of antibiotic treatment, the patient experienced near-complete relief of her respiratory symptoms., Lessons: Regardless of patient age, it is important to consider the possibility of HIES when a patient has recurrent eczema, skin and sinopulmonary infections, elevated serum immunoglobulin E levels, and eosinophilia. Early diagnosis and intervention are essential to improve prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility to Staphylococcal skin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES. Materials and Methods: A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis. Results: Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%). Mycobacterial infections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs * 8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12. Conclusions: The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant. Mycobacterial diseases were more frequent, compared to western literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saikia, Rawat, Minz, Suri, Pandiarajan, Jindal, Sahu, Karim, Desai, Taur, Pandrowala, Gowri, Madkaikar, Dalvi, Yadav, Lashkari, Raj, Uppuluri, Swaminathan, Bhattad, Cyril, Kumar, Shukla, Kalra, Govindaraj and Singh.)

Purpose of Review: This article reviews the ocular findings in patients with a myriad of autoimmune syndromes. This review will provide guidance and heighten awareness for the allergist or eye care provider to pay heed to the manifestations and treatments of autoimmune syndromes., Recent Findings: Autoimmune syndromes can present with varied manifestations on the ocular surface known to potentially cause significant visual morbidity. In particular, sterile corneal ulcers are the most devastating and common finding in uncontrolled autoimmune disease. Ophthalmic manifestations of autoimmune syndromes have been reported individually; however, herein we present a comprehensive review of typical and atypical syndromes that may present with sterile corneal ulceration., Summary: Autoimmune inflammatory syndromes are known to be associated with ocular surface inflammatory processes ranging from bothersome dry eye syndromes to vision-threatening sterile corneal ulceration. It is important to pay heed to the clinical presentation of common and uncommon presentations of the syndromes in the eye. We propose best practice for management of ocular surface disease in these clinical entities.

Background: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging., Objective: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort., Methods: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized., Results: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse., Conclusions: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Hyperimmunoglobulin E syndrome (HIGE) is considered as a phagocytic or a newly classified complex and heterogeneous primary immunodeficiency disease with symptoms such as increased levels of immunoglobulin E, eczema, and, recurrent lung and skin infections. In this paper, we have presented a rare case of this syndrome. A 9-year-old Iranian girl presented with a history of pruritic maculopapular rash who was eventually diagnosed as a case of HIGE. In her recent admission, she had dysphonia, stridor and huge cauliflower cutaneous lesions on her neck, finger and vocal cords, which did not respond to intravenous antibiotics, and ultimately required surgical removal.

Hyperimmunoglobulin E syndrome (HIES) is a rare heterogeneous primary immunodeficiency disorder characterized by infections of the lung and skin, elevated serum immunoglobulin E, and involvement of soft and bony tissues. Autosomal dominant HIES and related disorders are caused by defects in the Janus activated kinase-signal transducer and activator of transcription signaling pathway, leading to reduced numbers of T helper cell type 17 and impaired production of interleukin (IL)-17 A, IL-17 F, and IL-22. In addition, neutrophils have chemotactic defects, resulting in impaired responses at skin and lung sites. We report here a case of orofacial granulomatosis-like disease in a teenage boy ultimately found to have autosomal dominant HIES caused by a heterozygous mutation in the STAT3 gene., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We, herein, report a 23-year-old male with a rare inherited immunodeficiency disease, hyperimmunoglobulin IgE syndrome (HIES), who developed progressive multifocal leukoencephalopathy (PML) and lymphoma simultaneously. Primary immunodeficiency of the patient has remained undiagnosed until adulthood. PML is a severe demyelinating disease of the central nervous system caused by John Cunningham virus. HIES is a rare, inherited immunodeficiency characterized by high serum levels of IgE, recurrent staphylococcal infection, eczema, and hypereosinophilia. PML may accompany primary immunodeficiency syndromes, but the association with HIES is exceedingly rare. We discuss the imaging findings, medical management, and a review of related literature on primary immunodeficiency cases complicating with PML.

Objective: To describe the clinical features of hyper-IgE syndrome (HIES), with emphasis on refractory pulmonary cystic lesions as the initial presentation in adulthood. Methods: A case of HIES presenting with pulmonary cystic lesions in an adult patient was retrospectively analyzed. We used "hyper-IgE syndrome" as the Chinese keywords, "hyper-IgE syndrome, China" as the English keywords to retrieve the literature from Wanfang database/CNKI database and Pubmed database until April 2016. The clinical data were pooled and analyzed. Results: A 19 year old female patient was admitted to our hospital because of recurrent cough and expectoration as the chief complaint. Physical examination revealed broad nasal bridge and scoliosis, and chest CT showed gradually enlarged and increased cystic lesions. Laboratory studies demonstrated significantly increased blood eosinophils and serum level of total IgE, together with a definite chemotactic dysfunction of neutrophils. A further detection of STAT3 mutation was negative. The diagnosis of HIES was made and antibiotic treatment resulted in disease remission. Literature review found 45 reports including 37 in Chinese and 11 in English. Eight cases of adult HIES were reported, and all the patients were male, aging 18 to 31 years. Prolonged disease course, recurrent infection and formation of cystic lesions in the lungs were important features of HIES. Early diagnosis and treatment with specific antibiotics were important for improving outcome of the patients. Conclusion: Refractory pulmonary cystic lesions can be the initial presentation in adult HIES. Understanding of the clinical characteristics of HIES will be helpful to avoid misdiagnosis and improve prognosis.

The Hyperimmunoglobulin E syndrome (HIES) is a rare sporadic or autosomal dominant immune and connective tissue disorder characterized by chronic eczema, cutaneous abscesses, pneumonias, invasive infections, high levels of Immunoglobulin E, primary teeth retention and bone abnormalities. We report a 24-year-old male with a history of cutaneous abscesses and esophageal candidiasis. He was admitted due to a left gluteal cellulitis. During the fifth day of hospitalization he presented a distal necrosis of the fourth finger of the right hand. Laboratory results showed high levels of IgE and positive cryoglobulins. The patient was discharged and was admitted again five days later with a new gluteal abscess. IgE levels were even higher. Applying Grimbacher scale, the diagnosis of Hyperimmunoglobulin E syndrome was reached.

The hyper-immunoglobulin E (IgE) syndrome (HIES), also known as Job's syndrome is a rare primary immunodeficiency characterized by the clinical triad of recurrent staphylococcal abscesses of skin, recurrent cyst-forming pneumonia, and an elevated serum IgE level of > 2000 IU/ml. Although, most cases are sporadic, families with autosomal dominant (AD-HIES) and recessive (AR-HIES) traits have been reported. Very few articles were published previously on central nervous system abnormalities with definite neurologic manifestations which may vary from partial facial nerve paralysis to hemiplegia in children but Acute Disseminated Encephalomyelitis (ADEM) in a child with HIES hitherto has not been reported. Here we describe a 5-year-old male child with HIES who presented with neurologic manifestations of ADEM.

Purpose: Autosomal Dominant Hyper IgE Recurrent Infection Syndrome (AD-HIES) is caused by mutations in STAT3 and characterized by eczema, recurrent bacterial infections, and skeletal and connective tissue abnormalities. To further understand the minimal trauma fractures of AD-HIES, we examined bone mineral density (BMD) and laboratory markers of bone turnover., Methods: Patients with AD-HIES enrolled in a prospective natural history study were examined with dual x-ray absorptiometry (DEXA) scans and laboratory studies of bone metabolism. The number of fractures was recorded as well as clinical features of AD-HIES including scoliosis and retained primary teeth. Patients on medications with skeletal effects, including bisphosphonates, were examined separately., Results: Twenty-three AD-HIES children (6-18 years) and 33 AD-HIES adults (21-50 years) not receiving bone-active drugs were studied. Fourteen of the 23 children (61%) had histories of minimal trauma fractures, as did 26 of the 33 adults (79%). Osteopenia or osteoporosis was found in 79% of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures. Markers of bone metabolism did not correlate with minimal trauma fractures or BMD. Patients on bone-active medications had improved BMD, but still sustained fractures., Conclusions: Minimal trauma fractures and decreased BMD are common in AD-HIES. Low radial BMD is associated with fractures, but hip and spine BMD are not. Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.

Job's syndrome (Hyperimmunoglobulin E syndrome) is a rare congenital immune deficiency condition, manifested by local and system changes. A case of successful pregnancy in patient, suffering from this rare disease is presented. The possible complications during the course of pregnancy, delivery and puerperal period and therapeutic alternatives during pregnancy are discussed.

Hyper-IgE syndrome is a congenitally acquired primary immune deficiency condition. We report a case of possible hyper-IgE syndrome who presented with multiple cold skin abscesses and chest infection due to Staphylococcus aureus and hyper-IgE findings. Patient also had tricuspid valve acute bacterial endocarditis with purulent pericarditis which is very rare. This case is presented to highlight that early diagnosis and treatment in such cases decreases the mortality and morbidity in phagocytic disorders.

Hyper-IgE syndrome (HIES) is a rare idiopathic primary immunodeficiency. It is characterized by a triad of findings, including high levels of serum IgE, recurrent skin abscesses and pneumonia and leads to pneumatocele formation. The diagnosis of HIES is complicated by a diversity of clinical and immunological spectrums and a heterogeneous set of genetic defects. The National Institute of Health (NIH) developed a scoring system for HIES in which a score greater than 14 indicates a probable diagnosis. Our patient presented with recurrent multiple abscesses on her scalp, recalcitrant eczema, candida onychomycosis, alopecia universalis, and highly elevated levels of serum IgE. Using the NIH scoring system, a 30 total-point score in this patient indicated the likelihood of carrying the HIES genotype. To our knowledge, there are no specific treatments of HIES. The humanized recombinant monoclonal antibody against IgE, subcutaneous omalizumab, was successfully used in this patient.

Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin and lung infections. We report the first case of Coccidioides immitis meningitis in a patient with HIES. Coccidioides should be included in the differential diagnosis for central nervous system infections in HIES patients.

Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency characterized by high serum IgE, chronic eczematoid dermatitis, and recurrent extracellular bacterial infections. Two types of HIES have been reported: type 1 and type 2. Type 1 HIES displays abnormalities in multiple systems, including the skeletal, dental, and immune systems, whereas type 2 shows abnormalities confined to the immune system. We recently identified hypomorphic mutations in the signal transducer and activator of transcription 3 (STAT3) gene in type 1 HIES and a null mutation in the tyrosine kinase 2 (Tyk2) gene, accompanied by susceptibility to intracellular bacteria in type 2 HIES. Analyses of cytokine responses in both types of HIES revealed that severe defects in the signal transduction for multiple cytokines, including interleukin-6 and interleukin-23, are leading to impaired T-helper type 17 function. These findings suggest that HIES is caused by the defects in multiple cytokine signals and that the susceptibility to various infections in HIES is associated with the T-helper type 17 defect.

We are reporting on a 7-months-old boy with suspected hyper-IgE syndrome, presenting with a therapy resistant severe eczema and an overall reduction of in vitro cytokine production. Interferon-alpha (IFN-alpha) treatment resulted in a marked and stable clinical improvement and normalization of in vitro T-cell cytokine production, indicating a valid therapeutic potential of IFN-alpha as immunomodulating drug.

Summary: Cytokines play pivotal roles in immunity and inflammation, and targeting cytokines and their receptors is an effective means of treating such disorders. Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. These structurally unique protein kinases play essential and specific roles in immune cell development and function. One JAK, JAK3, has particularly selective functions. Mutations of this kinase underlie severe combined immunodeficiency, indicative of its critical role in the development and function of lymphocytes. Because JAK3 appears not to have functions outside of hematopoietic cells, this kinase has been viewed as an excellent therapeutic target for the development of a new class of immunosuppressive drugs. In fact, several companies are developing JAK3 inhibitors, and Phase II studies are underway. Mutations of Tyk2 cause autosomal recessive hyperIgE syndrome, and in principle, Tyk2 inhibitors might also be useful as immunosuppressive drugs. JAK2 gain-of-function mutations (V617F) underlie a subset of disorders collectively referred to as myeloproliferative diseases and phase 2 trials using JAK inhibitors are underway in this setting. Thus, we are learning a great deal about the feasibility and effectiveness of targeting Janus kinases, and it appears likely that this will be a fruitful strategy in a variety of settings.

Job's syndrome (hyperimmunoglobulin E syndrome) is a congenitally acquired primary immune deficiency. The primary host defense defect in Job's syndrome is impaired phagocytosis. Accordingly, patients with Job's syndrome have difficulties eradicating staphylococcal infections. A continuous, high-grade Staphylococcus aureus bacteremia with a cardiac valve vegetation is the hallmark of S. aureus acute bacterial endocarditis (ABE). ABE may be caused by methicillin-sensitive Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA). We report a case of Job's syndrome MRSA mitral valve ABE. Presumably because of impaired phagocytic function, his MRSA ABE was complicated by extensive metastatic septic complications manifested as brain abscess, multiple epidural abscesses, and multifocal vertebral osteomyelitis. The patient did not respond to 5 days of appropriately dosed linezolid and daptomycin and remained bacteremic because abscess drainage was not an option in this case and the continuous, high-grade MRSA bacteremia continued despite appropriate therapy. High-dose daptomycin (12 mg/kg intravenously every 24 hours) was given, and his MRSA bacteremia was rapidly terminated. Because daptomycin does not cross the blood-brain barrier in therapeutic concentrations, linezolid was used to treat the brain abscess. The extensiveness of infection in this case is remarkable and is probably related to impaired phagocytic function from Job's syndrome. High-dose daptomycin therapy rapidly cleared the bacteremia and cured the endocarditis and epidural abscesses/vertebral osteomyelitis. The patient was treated with 8 weeks of high-dose daptomycin therapy with no adverse effects. If MRSA and methicillin-sensitive S. aureus bacteremias are unresponsive to usually effective antistaphylococcal agents, and surgical drainage of abscesses and removal of infected devices are not clinically possible, then a prolonged, high dose of daptomycin is a therapeutic alternative in such situations. To the best of our knowledge, this is the first case of MRSA mitral valve ABE complicated by extensive epidural abscesses and vertebral osteomyelitis in a patient with Job's syndrome.

Bullous pemphigoid is an acquired immunobullous disorder affecting predominantly the elderly. It is very rare in children and exceptional in infants. Hyperimmunoglobulin E syndrome is a rare primary immunodeficiency characterized by a triad of high serum levels of polyclonal immunoglobulin E with peripheral eosinophilia, recurrent staphylococcal infections of the skin and lungs, and pruritic dermatitis. Variable associated features include coarse facies, cold cutaneous abscesses, and osteopenia. This report describes, to the best of my knowledge, the first instance of childhood bullous pemphigoid associated with hyperimmunoglobulin E syndrome in a 6-month-old boy.

Hyperimmunoglobulin E (Hyper IgE) syndrome, also described as Job's syndrome, is a rare primary immunodeficiency disease characterized by recurrent skin and respiratory tract infections, chronic eczematous dermatitis, skeletal abnormalities associated with markedly elevated serum IgE levels. Variable impaired T cell function is described in this disease, but no direct association between IgE levels or clinical manifestations with these abnormalities does exist. We report a case of a patient with recurrent staphylococcal cold abscesses, eczematous dermatitis and high serum IgE levels in which the treatment with Cyclosporine A seems to have a favorable effect.

The hyperimmunoglobulin E syndrome was discribed for Buckley, and it also called the Job syndrome. There are two types: dominant autosomal and recessive autosomal. It is a primary, rare and complex immunodeficiency, characterized clinically by recurrent skin abscesses for Staphylococcus aureus, recurrent pneumonia, and pneumatoceles, hypereosinophylia, high serum levels of immunoglobulin E (> 2,000 Ul/mL), early eczema and late loss of primary dentition. Recently a STAT3 mutation has been described as origin of dominant autosomal hyperimmunoglobulin E syndrome. Since 1972, 250 cases have been reported around the world. The diagnosis is done with the Grimbacher criteria and the prognosis depends on the opportune diagnosis and treatment. The incidence is same in women and men. The differential diagnosis is with allergic bronchopulmonary aspergillosis, chronic granullomatose disease, T cell lymphoma, and atopic dermatitis. The treatment is with prophylactic antibiotic, intravenous immunoglobulin or recombinant INF gamma.

Primary immunodeficiency diseases (PID) are associated with various autoimmune complications and several manifestations of autoimmunity can be seen in the disorders of T cells, B cells, phagocytes, and complement components. Acquired hemophilia is a rare entity in childhood. Although autoantibodies may develop in various forms of PID, Factor VIII (FVIII) inhibitors have not been described before. Herein, we present a case of acquired hemophilia resulting from FVIII inhibitors who had underlying undefined PID features suggestive of autosomal recessive hyper IgE syndrome. Our patient responded to corticosteroid treatment rather well and quickly, with an increased FVIII level and decreased FVIII inhibitors. However, FVIII inhibitor reappeared 7 months later, and disappeared spontaneously 4 months ago. Long-term and close follow-up is needed to observe the long-term prognosis in this child.

Hyper-IgE syndrome, a multi-system disorder affecting dentition, skeletal and immune systems and connective tissues, presents with recurrent infections and dermatitis. We report here the first case in Sri Lanka.

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cases seen at our institution and review the current literature. Patient 1 was an 18-month-old African American boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He had severely eczematous skin, ultimately complicated by eczema herpeticum. After treatment of systemic infections with culture-directed antibiotics, a brief course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15-year-old Caucasian boy with long-standing HIES. He has been maintained on a regimen of interferon gamma injections given 3 times weekly and monthly intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics, and low-dose fluconazole. He has occasional episodes of cold abscesses and sinusitis, but has had excellent control since institution of this regimen and has not experienced any adverse effects.

A case of atopic dermatitis (AD), recurrent infections, and elevated immunoglobulin E (IgE) level is presented. Clinical characteristics, pathophysiology, diagnosis, and management in this patient are reviewed. Clinical pearls and pitfalls include the following: (1) deep-seeded Staphylococcus aureus infections occur rarely in AD and should raise the possibility of immunodeficiency syndromes such as hyper-IgE syndrome (HIES); (2) HIES is characterized by a clinical triad consisting of elevated serum IgE levels, recurrent staphylococcal skin abscesses, and pneumonia with pneumatocele formation; (3) although serum IgE levels in AD have been noted to be as high as 10,000 IU/mL, severe cases of AD such as that presented here can exceed this range; (4) the efficacy of anti-IgE therapy in AD or HIES is unknown and may be limited by dosing requirements.

We describe the beneficial effects of treatment with cyclosporin A in a 10-year-old boy with hyperimmunoglobulin E and refractory nephrotic syndrome. The patient was initially resistant to steroid therapy with prednisolone alone. Additional therapy with cyclosporin A was then prescribed, effectively reducing levels of serum immunoglobulin E and preventing flare up of nephrotic syndrome.