Rheumatic manifestations of alkaptonuria: clinical, genetic and capillaroscopic characterisation of a referral centre cohort reveals new capillaroscopic marker of the disease

Abstract

Objectives: Alkaptonuria is a rare genetic disorder caused by the build-up of homogentisic acid, leading to its deposition in connective tissue. Previous studies have documented histopathological evidence of extracellular matrix and vessel wall deposits and neoangiogenesis in patients with alkaptonuria, as well as the possible role of dermoscopy in characterising macroscopically visible skin deposits. This proof-of-concept study aimed to describe the capillaroscopic changes in patients with alkaptonuria.

Methods: In this cross-sectional single-centre study, alkaptonuria patients were evaluated phenotypically, genetically, and with capillaroscopy. Capillaroscopic findings were compared to three control groups: healthy controls, patients with primary Raynaud's phenomenon and patients with systemic sclerosis.

Results: Ten alkaptonuria patients were included (60 % female, mean age 54.4 ± 12.2 years). All patients had skin and/or sclerae pigmentation and the majority (90 %) had musculoskeletal manifestations. One patient had a normal capillaroscopy. Blue-blackish deposits suggestive of homogentisic acid accumulation were observed in six patients, the majority of which were not visible to the naked eye. None of the patients from the three control groups had this capillaroscopic finding. Nine patients with alkaptonuria presented atypical, non-specific capillaroscopic changes. Notably, we observed a significantly higher prevalence of abnormally shaped capillaries compared both to healthy controls (70.0 % vs 20.0 %, p = 0.034) and to patients with primary Raynaud's phenomenon (70.0 % vs 20.0 %, p = 0.034), and of dilated capillaries compared to patients with primary Raynaud's phenomenon (50.0 % vs 13.3 %, p = 0.045).

Conclusions: This study is the first to document capillaroscopic changes in alkaptonuria patients, supporting the hypothesis of microcirculation damage in this disease and raising the question of a possible role of capillaroscopy as a diagnostic, prognostic, and disease monitoring tool in this condition.

Keywords: Alkaptonuria; Capillaroscopy; Metabolic disorder; Microcirculation; Rheumatology.