Pigmented Palmo-plantar Papules and Plaques.

A 50-year-old married woman, a product of a non-consanguineous marriage, presented with asymptomatic, progressive pigmented eruption of palms, fingertip and toes of 15 years duration. She also complained of dull aching low back pain associated with morning stiffness of 4 years duration. She denied the use of skin lightening creams or ayurvedic preparations. Her past medical and family history were unremarkable.

Cutaneous examination revealed blue-black elevated papules and plaques with pitting along the line of transgradience of the thumb and index finger of both hands [Figure 1]. Similar lesions and hyperpigmented macules were evident over the pulp of fingers, thenar eminence and bilateral big toes. No similar lesions were present at any other site and systemic examination was normal except for painful and restricted mobility of the lumbar spine. Routine hematological and biochemical profile of the patient was within normal limits. Radiography of dorso-lumbar spine revealed narrowing of intervertebral discs with calcification. Ultrasonography of the abdomen and electrocardiography were unremarkable. A specimen from palmar lesion was obtained for histopathology. Histopathological findings revealed a flattened epidermis and clumps of swollen and homogenized collagen bundles that appeared fragmented and contained yellowish-brown pigment, in the dermis. The pigment was also present separately in the dermis and stained black with methylene blue and Masson Fontana stain was negative for melanin.

Figure 1

Pigmented papules and plaques with pitting over the palms and digits

Further, darkening of patient's urine was evident on standing overnight, which confirmed the diagnosis of alkaptonuria.

Question

What is the diagnosis?

Answer

Diagnosis: Endogenous ochronosis (alkaptonuria [AKU]).

Discussion

AKU is a rare autosomal recessive inherited disorder, wherein deficiency of the enzyme homogenistic acid oxidase leads to the accumulation of homogentisic acid that is excreted in urine and is deposited as deep brown or ochre pigment in the mesenchymal tissues. As the disease progresses, tissue deposition of polymerized homogentisic acid eventually leads to the progressive degeneration of affected body systems.[12] This metabolic disorder has been attributed to a gene locus (AKU) on chromosome 3q.[3] The deposition in sclera (Osler sign), face and other sun exposed areas is often the first clue to the diagnosis.[14] The other sites of predilection include regions with high eccrine density like the genitals and cartilaginous tissue like pinnae and nose.[12] A few case reports and a recent series of five patients have reported palmo-plantar pigmentation as the presenting sign.[124] The preferential involvement of the latter site has been attributed to the relatively light color skin at this site in darker skin people and due to local stress and frictional factors.[14] Indeed it is pertinent to note that all patients reported till date have had dark color skin which may mask the pigment deposition over the more commonly afflicted photo-exposed sites.[14] Ochronotic pigment has been found to have affinity for collagen fibers. The latter is responsible for lesions, which akin to the present case, mimic marginal keratoderma.[4] The arthropathy is due to pigment deposition in articular cartilage, joint capsules, tendons and ligaments.[25] It generally involves the large joints and the dorso-lumbar spine with prominent intervertebral disc calcification.[124] Rarely, AKU manifests as cardiovascular disease, renal calculi and cholelithiasis.[25]

The diagnosis is based on characteristic clinical and histological findings and urine examination wherein alkanized urine, on exposure to air becomes dark black.[12] In doubtful cases, diagnosis may be confirmed by chromatographic demonstration of homogenistic acid in the serum and urine.[1] The treatment is directed towards decreasing the connective tissue damage by intake of low protein diet to limit the amount of phenylalanine and tyrosine generated and high doses of the anti-oxidants, analgesics and physiotherapy.[5] The anti-oxidants reported to be beneficial in experimental studies include ascorbic acid, phytic acid, taurine, ferulic acid and lipoic acid.[6] A regular cardiac follow up is advisable.[5]