Hyper-IgE syndrome
Description
● Introduction
➣Rarity: less than one case per million; around 250 cases have been reported globally.
➣Genetics:
• STAT3-HIES (AD-HIES, OMIM #102582): Stat3 gene (chromosome 17) dominant-negative mutations.
➣ Additional types include:
• DOCK8 mutations in HIES2 (AR-HIES) (OMIM #243700)
• ZNF341 mutations in HIES3 (OMIM #618282)
• IL6ST mutations in HIES4A and HIES4B (OMIM #619752 & #618523)
• IL6R mutations in HIES5 (OMIM #618944)
➣ Pathophysiology: decreased TH17 cells, impaired STAT3 activity, and impaired cytokine signalling lead to increased vulnerability to bacterial and fungal infections.
➣ Background: IgE was first identified as a cardinal characteristic in 1972.
● Clinical Characteristics:
➣ Immunologic/related to infection:
• Cold abscesses that occur often (mostly caused by Staphylococcus aureus).
• Recurrent pneumonia, which is frequently made worse by pneumatoceles.
• Candida on the mucosa.
• Skin rash onset: first week of birth.
• Elevated IgE (>1000 IU/mL, with the potential to exceed 100,000 IU/mL) and eosinophilia (>700 cells/µL).
➣ Extra-immune or non-immunologic manifestations
• Prominent forehead, deep-set eyes, wide nasal bridge, fleshy nasal tip, high-arched palate, prognathism, and increased inter-alar distance are all signs of facial dysmorphism.
• Skeletal: pathological fractures (~50%), osteopenia/osteoporosis, joint hyperextensibility, scoliosis, and retention of at least three primary teeth (~70%).
• Neurologic/Craniofacial: Arnold Chiari type 1 malformation, craniosynostosis.
• Vascular: aneurysms (coronary, cerebral, and aortic) and tortuosity/dilation of arteries.
• Risk of malignancy: increased risk of lymphomas.
➣ Lab results
• Extremely elevated IgE (10,000 IU/mL in the example).
• Eosinophilia.
• Regular IgG, IgA, and IgM.
● Case Overview:
➣ Patient: 37-year-old man who was diagnosed with recurring cold abscesses on his back and groin at the age of two.
➣ Clinical history:
• Several cold abscesses, some of which needed to be drained or incised.
• eczema-like rash, hyperpigmentation, and developmental problems (Down syndrome, autism).
• Recurrent respiratory and skin infections, as well as increasing consequences (loss of bladder and bowel control).
➣ Examinations:
• Eosinophilia, IgE: 10,000 IU/mL.
• Genetic confirmation: Invitae Hyper-IgE Panel shows a STAT3 mutation.
Anaemia, low RBC indices, increased ESR, and neutrophilia are blood test results.
• Imaging: minor scoliosis, tiny lung nodules, peri-bronchial thickening, cardiac echo with normal left ventricular function, and mild mitral leaflet thickening on the chest X-ray.
➣ Management:
• Antibiotics for infections and supportive treatment.
• Ascorbic acid, ferrous sulphate, megestrol acetate, Tylenol, and hydrocortisone taper are used to treat symptoms.
• Follow-up telehealth; patient looking into clinical trials.
● Diagnosis:
➣ Clinical suspicion: facial characteristics, eczema, history of recurring infections, and retained teeth.
➣ Laboratory indicators:
• Eosinophilia
• Increased IgE (>1000 IU/mL)
➣ STAT3 sequencing, the gold standard for genetic validation
➣ Other tests include:
• Imaging: bone density scans, CT (pneumatoceles), and chest X-rays;
• Flow cytometry for TH17 cells and STAT3 phosphorylation
➣ HIV and chronic granulomatous illness are examples of differential diagnosis.
Protocol
● Management:
➣ Supportive: early antibiotic treatment, prevention of recurring infections. Immunomodulation and new treatments:
• Stem cell treatment and bone marrow transplantation (rare, donor-dependent)
• The IL-4Rα antagonist dupilumab is being studied.
➣ Objectives: avoid infections, control side effects, preserve bone health, and keep an eye out for cancer.
● Typical Issues and Their Resolution:
➣ Hyperacute Problems and Early Identification
• Difficulty: Poorer results result from postponing the identification of symptoms and the start of treatment.
• Nursing Intervention: Nurses directly coordinate time-sensitive therapies such as thrombolytics, closely monitor for contraindications, continuously assess neurological function, manage airways, and activate emergency response systems and ensure prompt neuroimaging.
➣ Preventing Acute Phase Complications
• Challenge: Elevated risk of fever, hyperglycemia, pressure injury, deep vein thrombosis, and aspiration pneumonia.
• Nursing Intervention: Nurses regulate blood glucose and temperature, optimise oxygenation, manage haemodynamics, maintain airway patency, avoid infections and pressure ulcers by regular repositioning and early mobilisation, and use preventive measures to monitor for thrombotic consequences.
➣ Cognitive, Emotional, and Psychological Issues
• Difficulty: Following a stroke, patients frequently experience anxiety, sadness, and cognitive impairment, which impairs rehabilitation and lowers quality of life.
• Nursing Intervention: In order to meet the needs of patients and carers, nurses offer psychological support, screen for mood and cognitive disorders using instruments like the PHQ-9 and MoCA, provide counselling, make referrals to mental health services, and involve families in care planning. They also use support groups and specialised psychoeducation.
➣ Rehabilitation and Adherence Problems
• Difficulty: A lack of knowledge, drive, or support causes many patients to find it difficult to follow rehabilitation plans, which hinders functional recovery.
• Nursing Intervention: To encourage participation in therapy, nurses do routine follow-ups (including home visits and telemedicine), employ motivational interviewing, create customised care plans, inform patients and carers about the advantages of rehabilitation, and offer encouraging remarks.
Deficits in Communication (Aphasia/Dysphasia)
• Difficulty: Many stroke victims had difficulty speaking or understanding, which causes frustration and creates more obstacles to receiving care.
• Nursing Intervention: Nurses work with speech-language pathologists and reinforce communication techniques by using reduced language, organised routines, and augmentative and alternative communication technologies (such image boards).
➣ Nutritional Challenges
• Challenge: Following a stroke, dysphagia increases the risk of dehydration, malnourishment, and aspiration.
• Nursing Intervention: Nurses monitor nutritional status, monitor early swallowing assessments, coordinate hydration and adapted foods, consult with nutritionists and speech therapists, teach families safe eating habits, and facilitate temporary enteral feeding if necessary.
Encouraging Carers
• Difficulty: Families frequently experience emotional, physical, and financial hardship as a result of the unexpected weight of caregiving.
• Nursing Intervention: To support carer well-being, which tangentially enhances patient outcomes, nurses train and educate carers prior to discharge, offer continuous emotional support, link them to resources for support, provide respite care, and keep lines of communication open.
Notes
For more information visit 10.1097/MS9.0000000000001670
