Ochronosis Presenting as Methemoglobinemia

Abstract

Ochronosis is the blue-gray discoloration of collagen-containing tissues due to homogentisic acid (HGA) deposition, secondary to endogenous alkaptonuria or exogenous enzyme inhibition. In renal disease, accumulation of HGA in serum can cause methemoglobinemia. A 60-year-old woman with renal disease and anemia presented with 3 days of weakness and months of gray skin discoloration. Her hemoglobin was 8.1g/dl with 24.5% methemoglobin. Despite treatment with methylene blue, exchange transfusion, and continuous renal replacement therapy, the patient died. Autopsy revealed gray discoloration and ochronotic pigment in the ribs and cartilage. Based on these findings, the patient was diagnosed with ochronosis, suggestive of alkaptonuria, complicated by methemoglobinemia. The differential diagnosis for blue-gray skin discoloration includes argyria, methemoglobinemia, and ochronosis. This patient's clinical and autopsy findings suggested alkaptonuria complicated by methemoglobinemia due to progressive renal dysfunction. Development of methemoglobinemia in the setting of chronic skin discoloration and renal failure should prompt consideration of alkaptonuria.

Therapeutic whole blood exchange in the management of methaemoglobinemia: Case series and systematic review of literature

“…Our search yielded 365 citations (Figure ), of which 25 fulfilled our inclusion criteria (27 subjects) . Studies that mentioned exchange transfusion in the management of methaemoglobinemia, but failed to provide the details, were also not included .…”

“…Therapeutic exchange was performed either using automated (n = 7) or manual techniques (n = 5) . The amount of blood exchanged (data available from 24 subjects) ranged from 1000 to 11 700 mL (median 3000 mL).…”

“…Naphthalene balls, rasburicase, and chloroquine, were identified as the culprit agents in two patients each. Other reported causes included ochronosis, 35 benzene, 8 propanil, 28 aniline, 14 thinner material for paints, 26 co-trimoxazole, 22 and aminophenol. 33 The intent of overdose was often suicidal (n = 13, 40.6%) or accidental ingestion (n = 7, 21.9%).…”

“…In Therapeutic exchange was performed either using automated (n = 7) 10,23,27,[31][32][33][34] or manual techniques (n = 5). 8,15,16,20,35 The amount of blood exchanged (data available from 24 subjects) ranged from 1000 to 11 700 mL (median 3000 mL). The detailed description of the procedure employed and the kit used was provided in only one of the previously reported cases.…”

“…Of the 32 subjects included in the review, 26 (81.2%) survived. The cause of death was severe poisoning in two 19,21 ; while one patient each succumbed to multiorgan failure (in a subject with ochronosis) 35 and fulminant liver failure. 10 The cause of death was not reported in two subjects.…”