|Year : 2019 | Volume
| Issue : 2 | Page : 100-103
Endogenous ochronosis with keratoelastoidosis marginalis
R Mythreyi1, Adikrishnan Swaminathan2, Anuradha Priyadarshini2, Sudha Rangarajan2, S Murugan2
1 Department of Dermatology, Sri Ramachandra Medical College, Chennai, Tamil Nadu, India
2 Department of Dermatology Venereology and Leprosy, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
|Date of Web Publication||28-Nov-2019|
Dr. R Mythreyi
Department of Dermatology, Sri Ramachandra Medical College, Porur, Chennai - 600 116, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Endogenous ochronosis is a manifestation of alkaptonuria, a rare metabolic disease due to homogentisic acid oxidase deficiency. Darkened urine and arthropathy are the other two components that complete the triad of alkaptonuria. Pigmentation of skin, the presenting feature, is common over the face and ears. A few cases of pigmentation of the palms and soles are reported. Here, we report a case of endogenous ochronosis presenting as keratoelastoidosis marginalis, which is a rare manifestation.
Keywords: Alkaptonuria, endogenous ochronosis, gray pigmentation, keratoelastoidosis marginalis
|How to cite this article:|
Mythreyi R, Swaminathan A, Priyadarshini A, Rangarajan S, Murugan S. Endogenous ochronosis with keratoelastoidosis marginalis. Indian J Dermatopathol Diagn Dermatol 2019;6:100-3
|How to cite this URL:|
Mythreyi R, Swaminathan A, Priyadarshini A, Rangarajan S, Murugan S. Endogenous ochronosis with keratoelastoidosis marginalis. Indian J Dermatopathol Diagn Dermatol [serial online] 2019 [cited 2020 Jun 1];6:100-3. Available from: http://www.ijdpdd.com/text.asp?2019/6/2/100/271945
| Introduction|| |
Endogenous ochronosis develops due to alkaptonuria, which is an autosomal recessive disorder. Alkaptonuria is a rare inherited metabolic disease with an incidence of 1:250000–1:1000000. Equal incidence is seen in both sexes. Keratoelastoidosis marginalis (KEM) is a marginal keratoderma usually seen in older age group following recurrent trauma or friction. Endogenous ochronosis presenting as KEM is a rare entity with a handful of cases reported in the literature.
| Case Report|| |
A 62-year-old gentleman, a farmer by occupation, came to dermatology outpatient with complaints of gray-black-colored skin lesions over both the hands, feet, face, and bilateral ears for 6-year duration, along with blackish discoloration over both sclerae. History of joint pains presents for 10 years. The skin lesions were asymptomatic. No history of decreased vision. There was no use of hydroquinone-based depigmenting creams.
On examination, the patient was conscious and oriented. His vitals were normal. Cardiac, respiratory system, and per abdomen examination were normal. Dermatological examination showed multiple grayish – hyperpigmented, atrophic papules coalescing together over margins of fingers and palms of both hands and margins of the sole and feet [Figure 1] and [Figure 2]. Similar pigmentation was seen on dorsa of both hands, feet, chest, and bilateral pinna [Figure 3]. Diffuse slate gray pigmentation was seen on bilateral palms.
On slit-lamp examination, both eyes showed violaceous pigmentation over the sclera – between the limbus and both medial and lateral canthi [Figure 4].
Skeletal examination showed tenderness over the hip joint and both knee joints. Crepitus was present over both knee joints.
On evaluation of the patient, renal and liver function tests were normal. Urine sample on exposure to air turned black after sometime [Figure 5]. Screening of urine metabolites was positive for ammoniacal silver nitrate test for homogentisic acid.
Skin biopsy was done from the dorsum of the left hand. Histopathological examination showed hyperkeratosis and mild spongiosis in the epidermis, ochre-colored oval-to-banana-shaped fibers in the upper dermis with scant periadnexal and perivascular lymphocytic inflammation [Figure 6] and [Figure 7]. Short bundles of altered collagen and thick and fragmented elastic fibers were noted on Verhoeff–Van Gieson staining [Figure 8].
|Figure 6: Hyperkeratosis and mild spongiosis in the epidermis and ochre-colored oval-to-banana-shaped fibers in the upper dermis|
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|Figure 8: Verhoeff–Van Gieson stain showing thickened and fragmented elastic fibers|
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Based on these clinical features and investigation results, the patient was diagnosed to have endogenous ochronosis with KEM of hands. He was started on tablet Vitamin C 500 mg twice daily and was advised to have low-protein diet and regular follow-up with an orthopedician and an ophthalmologist.
| Discussion|| |
Alkaptonuria is a disorder of tyrosine and phenylalanine metabolism. The defect is found in the gene q21-23.60 region of chromosome 3. The deficiency of the enzyme homogentisate 1,2 dioxygenase results in an increased accumulation of homogentisic acid, which is rapidly excreted by the kidney. Homogentisic acid on exposure to air get oxidized and turn black which is clinically manifest as the dark urine on standing, staining diapers and underclothes, the earliest manifestation of alkaptonuria. Over time, the accumulation of homogentisic acid also leads to its polymerization and irreversible binding to collagen and cartilage causing discoloration of skin, ear, and ocular tissue., This is seen as ochre-colored bodies and hence termed as ochronosis. Ochronotic pigment is usually seen in the fourth decade. The blue-black pigmentation of the sclera and conjunctiva is known as Osler's sign., Vision can rarely be affected.
Ochronotic pigmentation with KEM of hands is a rare presentation with handful cases reported in the literature., Papular eruption is predominantly seen over radial aspect of index finger, first web space, and ulnar side of thumb as was present in our patient. KEM is an acquired condition as a result of prolonged ultraviolet exposure, repeated trauma, and friction. Fragmentation of elastic fibers is characteristic in histopathology. In alkaptonuria, irreversible binding of the homopolymeric oxidation products of homogentisic acid to collagen leads to inflammation and degeneration of collagen resulting in KEM like features. The involvement of the hands in ochronosis has been described in other patterns of marginal keratoderma such as acrokeratoelastoidosis, collagenous and elastotic marginal plaques of the hands, and marginal papular acrokeratoderma.
Morbidity in alkaptonuria is more often related to arthropathy. Typically large joints and the spine are favored which is similar to osteoarthritis. An increased risk of myocardial infarction with calcification and stenosis of aortic valves and coronaries has been recently identified. Calculi in the kidneys, urethra, and prostate are the other causes of concern.
The diagnosis of alkaptonuria is made clinically in the presence of ochronosis, joint involvement, and history of urine discolouration; it is confirmed by screening of urine for homogentisic acid using gas-liquid chromatography. Polymerase chain reaction screening for mutation could be done, but there is no proven correlation between the various mutations and phenotype severity.
Alkaptonuria requires a multispecialty approach for management. A diet low in proteins, especially of tyrosine and phenylalanine, minimizes the excretion of homogentisic acid. Administration of high doses of ascorbic acid (1 g per day) inhibits the polymerization of homogentisic acid and binding to collagen, thus reducing ochronotic pigment. A newer treatment approach is aimed at blocking the enzyme 4-hydroxyphenylpyruvate dioxygenase, which leads to the formation of homogentisic acid. Nitisinone is the drug in current use with this mechanism of action.
Regular monitoring for cardiac, urogenital tract, and ocular involvement is mandatory.,,
| Conclusion|| |
Endogenous ochronosis, a rare entity by itself, can sometimes present with unusual and rare clinical features as in our case. Clinicians should be aware of those manifestations to diagnose at the earliest and thereby screening for multisystem involvement and preventing the complications for the better quality of life.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]