Table 2.
Summary of treatment recommendations and considerations for manifestations of STAT3-HIES
| Dermatological | Recommendation | Indication/notes |
|---|---|---|
| Eczema | Emollients and antihistamines | Reduction of pruritus |
| Monoclonal antibodies (dupilumab, anti-IL-4; omalizumab, anti-IgE) | May also reduce rates of skin abscess [121] | |
| Staphylococcal colonization | Topical antiseptics (e.g., dilute bleach baths, swimming in pools with chlorine) | |
| Anti-staphylococcal spectrum antibiotics, e.g., twice-daily co-trimoxazole [50] | Monitor for antibiotic resistance, which is seen at increased rates [122] | |
| Mucocutaneous candidiasis | Topical antifungal treatment or daily azole antifungal prophylaxis | Warn patients of side effects such as medication interactions and photosensitivity (for voriconazole) |
| Pulmonary | ||
| Recurrent pulmonary infection | Offer twice-daily co-trimoxazole prophylaxis | Pneumonia is common, and predisposes to formation of bronchiectasis and pneumatoceles [123, 124] |
| Consider antifungal prophylaxis with mold-active azoles such as itraconazole in patients with parenchymal disease (bronchiectasis, pneumatocele) | Aspergillus confers significant mortality risk [125–127] | |
| CPA or ABPA may require prolonged antifungal therapy due to poor penetration into parenchymal lung disease | ||
| Consider immunoglobulin replacement | May reduce frequency of pneumonia, though data are limited [128] | |
|
Offer routine immunization schedules, including live vaccinations, with the exception of the 23-valent pneumococcal polysaccharide vaccine (PPSV) Offer booster vaccinations if specific subtherapeutic IgG are observed |
Avoid the 23-valent pneumococcal polysaccharide vaccine due to reports of significant local reaction, including skin necrosis [3] | |
| Monitor microbiological culture and sensitivities regularly | Some authors propose intravenous antibiotic therapy for Pseudomonas bronchiectasis exacerbations [43] | |
| Acute infective episode | High index of suspicion for complications, e.g., empyema |
Patients may lack fever or other evidence of systemic inflammation Operative management risks complications, e.g., bronchopleural fistula formation [43] |
| Extend spectrum to include gram-negative bacteria (e.g., Pseudomonas aeruginosa) and Aspergillus in parenchymal disease awaiting microbiologic studies | ||
| Parenchymal lung disease | Chest physiotherapy, airway clearance devices, and/or hypertonic saline nebulization to augment mucus clearance | May risk hemoptysis [43] |
| Bone and connective tissue | ||
| Minimal trauma fractures | Optimize bone health with vitamin D supplementation | Bisphosphonates have an unclear role [72] |
| Monitor bone mineral density | May not predict risk of fracture, though a reduced z-score in the distal radius may be informative [72] | |
| Scoliosis | Monitor for development through adolescence | |
| Delayed exfoliation of primary dentition | Regular surveillance through childhood and adolescence, and consider removal | Consider removal to allow eruption of secondary teeth [77] |
| Vascular | ||
| Coronary arterial disease | Optimize modifiable risk factors (e.g., hypertension, hyperlipidemia) | |
| Consider antiplatelet agents, e.g., for primary prevention [129] | May risk hemoptysis, particularly if significant parenchymal lung disease or pulmonary arterial aneurysm is present | |
| Other arterial aneurysms | Surveillance every 3–5 years [91] | Management of asymptomatic aneurysms is challenging, due to limited data on their natural history and the implicit risk of intervention |
| Reproductive health and pregnancy | ||
| Contraception | Consider medication interactions when offering pharmacological contraception | E.g., combined oral contraceptive with azole antifungals |
| Pre-conception | Offer genetic counseling | |
| Pregnancy | Consider cessation of antimicrobial prophylaxis [130, 131] | Risk of teratogenicity |
| Low threshold for presentation with pulmonary symptoms | Pregnancy may exacerbate pulmonary disease | |