A Case of Alkaptonuria Diagnosed in the 6^th Decade – A Clinico-Dermoscopic-Histopathological View

Sir,

Alkaptonuria (AKU) is a rare autosomal recessive disorder of tyrosine metabolism caused by accumulation of homogentisic acid (HGA) in the connective tissues.[1] It presents with characteristic dark urine, ochronosis and systemic manifestations. We present a case of Alkaptonuria presenting in the 6^th decade for its rarity and to emphasise the role of dermatologists in the diagnosis with clinico-dermoscopic-histopathological correlation.

A 60-year-old man presented with asymptomatic lesions on the palms for 15-20 years. Previously diagnosed as allergic contact dermatitis, considering his occupation as a teacher, he was treated with topical corticosteroids. He was wheelchair bound since 2 decades due to arthritis. Physical examination revealed bluish keratotic papules, patches and crateriform plaques on the sides of fingers, thenar and hypothenar eminences [Figure 1a], greyish blue discoloration on malar area [Figure 1b], ear pinna and sclera. Urine showed progressive darkening on standing [Figure 1c]. Dermoscopy (using DermLite 3 dermoscope - 10× magnification) of the hand lesions showed white globular structure and greyish-blue areas [Figure 2]. Considering clinical differential diagnosis of ochronosis and argyria, further work up was done.Otoscopy showed black discoloration of tympanic membrane [Figure 3a]. Urine spectrophotometry was positive for homogentisic acid (elevation factor - 156.30). X-ray of the spine, knees, feet and wrist showed degenerative changes [Figure 3b]. Skin histopathology showed epidermal thinning and deposition of oval brown pigment material (ochre bodies) with collagen degeneration in dermis [Figure 4]. These constellation findings permitted diagnosis of AKU. Coordination of multispecialty care and a high dose of Vitamin C (1000 mg OD) were recommended.

Figure 1.

Clinical Image of Alkaptonuria Showing (a) Greyish-Blue Papules and Plaques on Hands, (b) Bluish Discoloration of Nose and Sclera (Osler's Sign),(c) and Darkening of Urine Upon Standing

Figure 2.

Dermoscopy of the Crateriform Plaques Displaying (a) White Globular Structures (Red Arrow) And Greyish-Blue Structureless Areas (Yellow Arrow), (b) Dermoscopy of the Palm Displaying Greyish-Blue Areas

Figure 3.

Investigations Done for Alkaptonuria Showing (a) Otoscopy-Blackish Discoloration of Tympanic Membrane, (b) X-Ray Spine Showing Intervertebral Disc Calcification, Reduced Disc Space and Bridging Osteophytes (b)

Figure 4.

Skin Histopathology Showing Oval Brown Pigment Material (Yellow Arrow) with Collagen Degeneration in Dermis (H and E Stain - 20×)

The incidence of AKU is 1 in every 250,000 to 1 million live births making it rare condition.[2] It is caused by mutations in the HGA dioxygenase (HGD) gene that encodes HGD, an enzyme in the tyrosine degradation pathway. This causes accumulation of HGA and its pigmented oxidative products in the connective tissue, urine and sweat. Pigment deposition in the dermis that clinically appears blue-black in colour is called ochronosis. Ochronosis initially becomes evident in the sclera (Osler's sign) and ears after 3^rd decade.[3] Other manifestations include dusky discoloration of hands and azure lunulae. Degenerative collagenous plaques of the hands is characterized by bandlike coalescing, crateriform papules on the sides of hands. This occurs due to degeneration of collagen fibres. Our case highlights this unique pattern which is described only in a few case reports.[3,4]

The most prominent internal manifestation of AKU is degenerative arthritis (predominantly large joints and spine) beginning in third decade.[2] HGA in the urine oxidizes and darkens on exposure to air or with an alkalizing agent. Dark staining of diapers usually prompts investigation early in life. The diagnosis relies on detection of elevated HGA levels in urine. Deposition of HGA also occurs in the kidney, bladder, prostate and cardiac valves.

Our dermoscopic findings of AKU are similar to the observation made by Ankad et al.[5] They explained that the greyish-blue area corresponds to noncellular ochre bodies in the dermis. White globular structures correspond to fibroplasia in the dermis. These findings correlate with the histopathological picture of AKU. Dermoscopy can be a useful non-invasive tool to differentiate AKU from exogenous ochronosis, lichen sclerosis, melanoma, etc.[5]

Treatment options are directed at managing complications. Vitamin C and dietary restriction of phenylalanine and tyrosine have not been found to be efficient. Nitisinone, approved for treatment of tyrosinemia type I, is currently under investigation as a potential treatment.[2]

An incidental cutaneous observation could be a marker of a disease masquerading as different diseases. This case of AKU, though present since birth and manifesting for years, was being treated as dermatitis and arthritis. Asymptomatic bluish pigmented plaques and patches could be a diagnostic clue to alkaptonuric ochronosis, which can be aided by dermoscopy and histopathological examination.

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Conflicts of interest

There are no conflicts of interest.