Dermatologic manifestations of hereditary hemochromatosis: A systematic review

Abstract

Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.

FIGURE 1

The PRISMA flow chart of study selection for inclusion in the systematic review.

FIGURE 2

Distribution of countries (a) and timeline of the included studies (b).

FIGURE 3

Description of the included studies based on their population (a) and methodology (b).

FIGURE 4

Illustration of dermatologic lesions in the hereditary hemochromatosis population in our review.