RESEARCH - Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain

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Arthritis Rheum. 2004 Nov;50(11):3698-701.

Minocycline-induced hyperpigmentation masquerading as alkaptonuria in

individuals with joint pain.

Suwannarat P, Phornphutkul C, Bernardini I, M, Gahl WA.

Section on Human Biochemical Genetics, National Human Genome Research

Institute, NIH Building 10, 10 Center Drive, Bethesda, MD 20892, USA.

suwannar@...

Alkaptonuria, a rare autosomal-recessive disorder caused by mutations in the

HGD gene and a deficiency of homogentisate 1,2-dioxygenase, is characterized

by accumulation of homogentisic acid (HGA), ochronosis, and destruction of

connective tissue resulting in joint disease. Certain medications have been

reported to cause cutaneous hyperpigmentation resembling that of

alkaptonuria. We present 5 such cases. Eighty-eight patients with a possible

diagnosis of alkaptonuria were examined at the National Institutes of Health

Clinical Center between June 2000 and March 2004. The diagnosis of

alkaptonuria was confirmed or ruled out by measurement of HGA in the urine.

Five patients with findings consistent with ochronosis, including pigmentary

changes of the ear and mild degenerative disease of the spine and large

joints, were diagnosed clinically as having alkaptonuria, but the diagnosis

was withdrawn based on normal urine HGA levels. All 5 patients were women

who had taken minocycline for dermatologic or rheumatologic disorders for

extended periods. Minocycline-induced hyperpigmentation should be considered

in the differential diagnosis of ochronosis. This could be of increased

significance now that minocycline and other tetracyclines have been proposed

as therapeutic options for rheumatoid arthritis, bringing a new population

of patients with ochronosis and arthritis to medical attention with the

potential, but incorrect, diagnosis of alkaptonuria.

PMID: 15529343

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15529343 & itool=iconabstr & query_hl=4

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