The Spectrum of Epidermolysis Bullosa in KwaZulu-Natal, South Africa

Antoinette Chateau; Thirona Naicker; Cassandra Bruce-Brand; Johann Schneider; Colleen Aldous; Ncoza Dlova; Hui-Ching Cheng; Pei-Chi Lin; Hsin-Yu Huang; Chao-Kai Hsu; John A McGrath

doi:10.1111/ijd.17843

The Spectrum of Epidermolysis Bullosa in KwaZulu-Natal, South Africa

Int J Dermatol. 2025 May 14. doi: 10.1111/ijd.17843. Online ahead of print.

Authors

Antoinette Chateau^{1

2}, Thirona Naicker³, Cassandra Bruce-Brand^{4

5

6}, Johann Schneider^{4

5}, Colleen Aldous⁷, Ncoza Dlova², Hui-Ching Cheng⁸, Pei-Chi Lin⁸, Hsin-Yu Huang⁸, Chao-Kai Hsu⁸, John A McGrath⁹

Affiliations

¹ Department of Dermatology, Grey's Hospital, Pietermaritzburg, University of KwaZulu-Natal, School of Clinical Medicine, Durban, South Africa.
² Department of Dermatology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
³ Department of Paediatrics, Medical Genetics, School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa.
⁴ Division of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁵ National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa.
⁶ JDW Pathology, Cape Town, South Africa.
⁷ University of KwaZulu-Natal, School of Clinical Medicine, Durban, South Africa.
⁸ Department of Dermatology, National Chun Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁹ St John's Institute of Dermatology, King's College, London, UK.

PMID: 40369731
DOI: 10.1111/ijd.17843

Abstract

Background: Epidermolysis bullosa (EB) is a rare, heterogeneous genodermatosis characterized by skin fragility due to inherited defects in genes encoding proteins that maintain epidermal-dermal integrity. The severity and complications of EB vary by subtype, and no cure currently exists. The epidemiology is unknown in South Africa.

Methods: This prospective observational study in KwaZulu-Natal correlated African Zulu EB patients' phenotypic features with genotypic and histological findings. Whole-exome sequencing, electron microscopy, and immunofluorescence mapping were used to identify EB subtypes.

Results: Fourteen of the 15 patients recruited initially were confirmed to have EB, while one was excluded due to poor clinicopathological-genetic correlation. Junctional EB (JEB) was identified in 11 patients, with 10 cases linked to a recurrent homozygous pathogenic variant in LAMB3, causing severe JEB, and one to ITGA3 with an unusual variant of interstitial lung disease, nephrotic syndrome, and EB (ILNEB). Two patients had autosomal dominant EB simplex, both with heterozygous KRT14 variants, and one had dominant dystrophic EB associated with a heterozygous COL7A1 variant. Eleven patients presented during the neonatal period, with a mean survival of four weeks, highlighting a high mortality rate, especially in the severe JEB cases. The cohort exhibited a balanced sex distribution, with no clear cases of consanguinity observed.

Conclusion: JEB, with a recurrent pathogenic variant in LAMB3, emerged as the predominant subtype among African Zulu patients, underscoring the critical need for early diagnosis and tailored management strategies in resource-limited settings. Integrating clinicopathological and genetic data is essential for accurate diagnosis and prognosis, emphasizing the importance of advanced diagnostic tools in improving outcomes for EB patients in South Africa.

Keywords: South Africa; Zulu African patients; electron microscopy; epidermolysis bullosa; immunofluorescence mapping; skin of color; whole‐exome sequencing.

Grants and funding

College of Health Sciences, University of KwaZulu-Natal