Ochronosis

S Quyoom, M Jehangir, I Hassan, Q Masood

 Department of Dermatology, SKIMS Medical College, Bemina, Srinagar, India

Correspondence Address:
S Quyoom
Khalidabad, Baghat P.O. Sanatnagar, Srinagar J&K. 190005
India

Introduction

Alkaptonuria is a rare metabolic disorder first described by Garrod in 1902.[1] It is characterized by a deficiency in the enzyme homogentesic acid oxidase, which is normally found in the liver and kidney.

Ochronosis describes the deposition of a melanin like brownish black pigment derived from the oxidized product of homogentesic acid (benzoquinone acetic acid) in connective tissues and cartilage. An exogenous ochronosis can also occur from hydroquinone containing skin bleaching creams.[2]

The classical autosomal recessive condition presents with alkaptonuria, arthritis and distinctive cutaneous pigmentation (ochronosis). One of the earliest signs is thickening of ear cartilage associated with blue-black or grey-blue in discolouration. The pinna feels noticeably thickened and flexible and in later stages there may be gross calcification. Cerumen is often brown or jet black. Besides the cutaneous involvement cardiovascular renal, ocular and musculoskeletal system are significantly affected. The intervertebral discs, larynx, tracheal rings and articular cartilages are jetblack as if "dipped in Indian ink".

Case Report

A 40-year-old man was admitted in Dermatology ward for evaluation of progressive facial hyperpigmentation of 6 years duration. History revealed that the patient had been passing urine, which would leave a black precipitate at sites of contact since childhood. He was the product of consanguineous marriage and was third in birth order. The other sibs were all apparently normal. Patient had been suffering form low backache, arthritis of the knees, hip and small joints of hands and feet for the past 10 years.

Clinical examination revealed Osler′s sign in the sclera, ochronotic pigmentation of the skin over palms, nose, cheeks and forehead. Patient also had active arthritis of knees. Routine haemogram, chest X-ray, renal function tests and liver function tests were within normal limits. Spinal X-ray, renal function tests and liver function tests were within normal limits. Spinal X-ray revealed pathogenic changes of ochronosis.

Biochemical examination of the urine with ferric chloride, Benedicts reagent and silver nitrate were positive, E.C.G. and U.S.G. abdomen were normal. X-ray of knees showed arthritis with degenerative changes. A skin biopsy showed deposition of ochronotic pigment in the dermis with disruption of collagen.

Besides the symptomatic treatment the patient was put on tablet vitamin C 1gm tid, once the diagnosis of ochronosis was established. Subsequently patient was referred to the orthopedic department where he was operated upon both the knees.

Discussion

The metabolic disorder of alkaptonuria has recently been attributed to the gene locus (AKU) on chromosome 3q.[4] Three forms namely the hereditary, the acquired and the exogenous forms have been recognized.[2] Our patient presented with classical sequence of events with cutaneous hyperpigmentation, arthritis and eye changes occurring in fourth decade while AKU had been present since childhood.[3]

The arthritis generally involves the spine, knee joints, shoulder joints and hip joints. Small joint involvement of hands and feet is unusual. Osteoarthritis is common. Pathological fractures are infrequent though rupture of intervertebral discs occurs. Renal calculi, cholelithiasis, prostatic calculi and ochronotic pigmentation of tendons have also been reported. Myocardial infarction is a common event in hereditary ochronosis as marked atherosclerosis is common. Thus ochronosis results in a near normal life span with morbidity due to the arthritis occurring in the fourth decade as illustrated in our patient.

Diagnosis in our patient was established by the classical clinical features, pathognomic spinal X-ray, skin histology and urinary biochemical findings.

Acquired ochronosis does not present as classical temporal pattern as hereditary ochronosis and exogenous ochronosis do not have alkaptonuria, arthritis or the systemic feature of hereditary ochronosis.

Osler′s sign as illustrated in our patient is due to deposition of ochronotic pigment in the sclera at site of insertion of the extra ocular muscles. Though similar lesions have been described in melanoma, bilateral involvement and other correlated manifestations differentiate the diagnoses.

Since the major damage induced by the metabolic defect is hyperpigmentation and joint changes, treatment is directed towards decreasing connective tissue damage by high doses of ascorbic acid (anti oxidant), by analgesics and physiotherapy for the arthropathy. A low protein diet limiting the amount of phenylalanine and tyrosine is not practical as a long-term measure although it could be used intermittently.[5]

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