Clinical characteristics of pediatric cutaneous mastocytosis and the association with allergic comorbidities and inborn errors of immunity

Abstract

Objective: Cutaneous mastocytosis (CM) is the most common form of mastocytosis in childhood; however, data on its clinical course and associated allergic and immunologic features remain limited. This study aimed to characterize the clinical phenotype of pediatric CM and to evaluate the frequency of concomitant allergic diseases and inborn errors of immunity (IEI). Methods: This retrospective study included 17 pediatric patients diagnosed with CM between 2007 and 2025. Demographic characteristics, clinical findings, laboratory parameters, allergic sensitization, immunologic evaluation, and follow-up outcomes were systematically analyzed. Results: The cohort showed a male predominance (64.7%), with a median age at symptom onset of 14.2 months. Maculopapular cutaneous mastocytosis was the most frequent subtype (82.3%), followed by diffuse CM and solitary mastocytoma. During a median follow-up of 4.5 years, 11.2% of patients achieved complete regression, 47.0% showed partial regression, 35.2% remained stable, and 5.8% exhibited progression. No cases of systemic mastocytosis, anaphylaxis, or mortality were observed. Eosinophilia was present in 23.5% and hepatosplenomegaly in 11.7% of patients, without evidence of organ dysfunction. Serum immunoglobulin levels and vaccine responses were within normal ranges in all evaluated patients, and no IEI was identified. Elevated IgE levels were detected in 17.6%, while allergic sensitization was documented in 29.4%. Allergic comorbidities were observed in 41.1% of patients, most commonly allergic rhinitis. Conclusion: Pediatric CM predominantly presents as an early-onset, skin-limited disease with a favorable and often regressive clinical course. The frequency of allergic diseases and sensitization does not appear to be increased compared to the general population, and humoral immune function remains preserved. These findings support a selective, clinically driven approach to immunologic evaluation rather than routine screening in children with CM.

Keywords

• Cutaneous Mastocytosis
• Inborn Errors of Immunity
• Allergic Diseases
• Urticaria Pigmentosa
• Comorbidity
• Pediatric
• Primary Immunodeficiency

Pediatrik Kutanöz Mastositozun Klinik Özellikleri ve Alerjik Komorbiditeler ile Doğuştan Bağışıklık Kusurları Arasındaki İlişki

Abstract

Amaç: Kutanöz mastositoz (KM), çocukluk çağında mastositozun en sık görülen formudur; ancak klinik seyri ile ilişkili alerjik ve immünolojik özelliklere dair veriler sınırlıdır. Bu çalışmada pediatrik KM hastalarının klinik fenotipinin tanımlanması ve eşlik eden alerjik hastalıklar ile doğuştan bağışıklık yetmezliklerinin (IEI) sıklığının değerlendirilmesi amaçlanmıştır. Yöntemler: Bu retrospektif çalışmaya 2007–2025 yılları arasında KM tanısı alan 17 pediatrik hasta dahil edildi. Demografik özellikler, klinik bulgular, laboratuvar parametreleri, alerjik duyarlanma, immünolojik değerlendirme ve izlem sonuçları sistematik olarak analiz edildi. Bulgular: Olguların %64,7’si erkek olup, semptom başlangıç yaşı medyan 14,2 ay idi. En sık görülen alt tip makülopapüler kutanöz mastositoz (%82,3) olup, bunu diffüz KM ve soliter mastositom izledi. Medyan 4,5 yıllık izlem süresinde hastaların %11,2’sinde tam regresyon, %47,0’sinde parsiyel regresyon gözlenirken, %35,2’si stabil seyretmiş ve %5,8’inde progresyon saptanmıştır. Sistemik mastositoz, anafilaksi veya mortalite izlenmemiştir. Eozinofili hastaların %23,5’inde, hepatosplenomegali ise %11,7’sinde saptanmış olup organ disfonksiyonu gözlenmemiştir. Tüm hastalarda immünoglobulin düzeyleri ve aşı yanıtları normal sınırlarda bulunmuş, hiçbir hastada IEI saptanmamıştır. Yüksek IgE düzeyi %17,6 oranında görülürken, alerjik duyarlanma %29,4 olarak belirlenmiştir. Hastaların %41,1’inde eşlik eden alerjik hastalık bulunmuş olup en sık alerjik rinit saptanmıştır. Sonuç: Pediatrik KM genellikle erken başlangıçlı, deri ile sınırlı ve iyi prognozlu bir hastalık olup çoğunlukla stabil veya regrese olan bir seyir göstermektedir. Alerjik hastalık ve duyarlanma sıklığı genel popülasyona kıyasla artmış görünmemekte, humoral immünite korunmuş olarak izlenmektedir. Bu bulgular, KM’li çocuklarda rutin immünolojik tarama yerine klinik bulgulara dayalı seçici bir yaklaşımın daha uygun olduğunu desteklemektedir.

Keywords

• Kutanöz Mastositoz
• Doğuştan Bağışıklık Kusurları
• Alerjik Hastalıklar
• Ürtikerya Pigmentoza
• Komorbidite
• Pediatrik
• Primer İmmün Yetmezlik.

References

1. 1.Hartmann K, Escribano L, Grattan C, et al.Cutaneous manifestations in patients withmastocytosis: consensus report of the EuropeanCompetence Network on Mastocytosis; theAmerican Academy of Allergy, Asthma &Immunology; and the European Academy ofAllergology and Clinical Immunology. J Allergy ClinImmunol. 2016;137:35-45.
2. 2.Valent P, Akin C, Sperr WR, et al. New insights intothe pathogenesis of mastocytosis: emergingconcepts in diagnosis and therapy. Annu Rev Pathol:Mechanisms of Disease. 2023;18:361-86.
3. 3.Khoury JD, Solary E, Abla O, et al. The 5th editionof the World Health Organization classification ofhaematolymphoid tumours: myeloid andhistiocytic/dendritic neoplasms. leukemia.2022;36:1703-19.
4. 4.Schaffer JV. Pediatric mastocytosis: recognitionand management. Am J Clin Dermatol. 2021;22:205-20.
5. 5.Kaakati RN, Khokhar D, Akin C. Demographics,Types of Patient-Reported Allergic Diseases, andAnaphylaxis in Mastocytosis: A Single-Center US Experience. J Allergy Clin Immunol Pract. 2025;13:398-406.
6. 6.Olivieri B, Bonadonna P. Mast cell conditions anddrug allergy. Ann Allergy Asthma Immunol.2025;135:521-9.
7. 7. Geme JWS: Nelson textbook of pediatrics: Elsevier;2020.
8. 8.Bayram RO, Özdemir H, Emsen A, Daği HT, ArtacH.Reference ranges for serum immunoglobulin(IgG, IgA, and IgM) and IgG subclass levels in healthychildren. Turk J Med Sci. 2019;49:497-505.

9. 9.Özdemir Ö, Savaşan S. Cutaneous mastocytosis inchildhood: An update from the literature. J Clin PractRes. 2023;45:311.
10. 10.Durmaz AM, Özdemir Ö. Clinical spectrum ofpatients diagnosed with childhood mastocytosis: aretrospective single center experience. Eur AnnAllergy Clin Immunol. 2025;57:120-7.
11. 11. Rydz A, Lange M, Ługowska-Umer H, et al. DiffuseCutaneous Mastocytosis: A Current Understandingof a Rare Disease. Int. J. Mol. Sci. 2024;25:1401.
12. 12.Guerrer BL, Morgan MAP, Muzzolon M, et al.Burden of childhood cutaneous mastocytosis:Severity and caregivers’ quality of life. J Allergy ClinImmunol Pract. 2026;14:283-5. e1.
13. 13.Madigan LM, Boggs NA, Rets AV, et al.Mastocytosis in the Skin: Approach to Diagnosis,Evaluation, and Management in Adult and PediatricPatients. Am J Clin Dermatol. 2025;26:499-510.
14. 14.Hermans MA, Pasmans SG, Arends NJ, et al.Histopathological characteristics are instrumentalto distinguish monomorphic from polymorphicmaculopapular cutaneous mastocytosis in children.CED. 2022;47:1694-702.
15. 15.Gurnee EA, Johansen ML, Phung TL, et al.Pediatric maculopapular cutaneous mastocytosis:Retrospective review of signs, symptoms, andassociated conditions. Pediatr dermatol.2021;38:159-63.
16. 16.Crupi F, Caroprese J, Mannelli F. Defining“Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics insystemic mastocytosis. Frontiers in Allergy.2025;6:1592001.
17. 17.Leguit RJ, Wang SA, George TI, Tzankov A, OraziA.The international consensus classification ofmastocytosis and related entities. Virchows Archiv.2023;482:99-112.
18. 18.Madigan LM, Boggs NA, Rets AV, et al.Mastocytosis in the Skin: Approach to Diagnosis,Evaluation, and Management in Adult and PediatricPatients: LM Madigan et al. Am J Clin Dermatol.2025:1-12.
19. 19.Voss M, Kotrba J, Gaffal E, Katsoulis-Dimitriou K,Dudeck A. Mast cells in the skin: defenders ofintegrity or offenders in inflammation? Int. J. Mol.Sci. 2021;22:4589.
20. 20.Gomez G. Current strategies to inhibit highaffinity FcεRI-mediated signaling for the treatmentof allergic disease. Front Immunol. 2019;10:175.
21. 21.James AE, Abdalgani M, Khoury P, Freeman AF,Milner JD. TH2-driven manifestations of inbornerrors of immunity. J. Allergy Clin. Immunol.2024;154:245-54.
22. 22.Dudeck A, Köberle M, Goldmann O, et al. Mastcells as protectors of health. J Allergy Clin Immunol.2019;144:S4-S18.
23. 23.Makovoz A, Cousins KL, Dominguez Aldama LN,et al. Assessment of low immunoglobulin levels andclinical manifestations in patients withmastocytosis. J Allergy Clin Immunol Glob.2023;2:105-10.
24. 24.Jørgensen MP, Øvlisen AK, Jensen JF, et al.Prevalence and incidence of mastocytosis in adults:a Danish nationwide register study. Eur J Epidemiol.2025;40:43-53.
25. 25.Brockow K, Plata-Nazar K, Lange M,et al.Mediator-related symptoms and anaphylaxis inchildren with mastocytosis. Int. J. Mol. Sci.2021;22:2684.
26. 26.Jarkvist J, Brockow K, Gülen T. Low frequency ofIgE-mediated food hypersensitivity in mastocytosis.J Allergy Clin Immunol Pract. 2020;8:3093-101.
27. 27.Carter MC, Metcalfe DD, Matito A, et al. Adversereactions to drugs and biologics in patients withclonal mast cell disorders: A Work Group Report ofthe Mast Cells Disorder Committee, AmericanAcademy of Allergy, Asthma & Immunology. JAllergy Clin Immunol. 2019;143:880-93.