Ochronotic arthritis

Ochronotic arthritis

1. OCHRONOTIC ARTHRITIS Dr.PONNILAVAN SOURCE – TUREK Page - 275

2. OCHRONOSIS- Termed by Virchow Ochre – greek – yellow discoloration Two types – Endogenous– due to Hydroxyquinine ( topical) Exogenous

3. ALKAPTONURIA /Black urine d/s  AR, was 1st described by Sir Archibald Edward Garrod in 1902.

4. In 1908, Garrod coined the term ′inborn error of metabolism′ and proposed that alkaptonuria resulted from the deficiency of an enzyme that normally splits the aromatic ring of homogentisic acid.   Chromosome 3q

5. 1 st inborn error detected Belong to Garrod’s tetrad ( Alkaptonuria , albinism, pentosuria , cystinuria )

6. Epidemiology P revalence of AKU is 1 case in 250 000–1 000 000 births. H ighest prevalence is in Slovakia where up to 1 in 19 000 are affected

7. Musculoskeletal manifestations of AKU.  O steopenia /osteoporosis T endinopathy A rthropathy

8. D eficiency of the enzyme homogentisic acid oxidase   Increased levels of homogentisic acid (an intermediate metabolite of phenylalanine and tyrosine metabolism) resulting in

9. H omogentisic acid---  OXIDIZED Benzoquinone acetate- polymerised to alkaptone bodies Deposition of alkaptone bodies lead to a bluish-black discoloration of the cartilage as well as degeneration, inflammation, and calcification of the tendons, ligaments, intervertebral discs, and large joints and increased bone resorption .

10. A brittle and fragmented cartilage forms and leads to aberrant loading of the subchondral bone ..   These fragments then adhere to the synovial membrane and cause fibrosis or chondromatosis , leading to ochronotic arthropathy

11. Patients are typically asymptomatic in childhood. However , during the second to third decade of life, ochronosis may begin to manifest as a blue or brown pigmentation within the ear cartilage or the sclera; stones (renal, prostatic, gall bladder, and salivary glands); back or peripheral joint pain; rupture of the tendons, muscles, or ligaments; renal failure; osteoporosis; or fractures

12. Ochronotic tendinopathy most commonly affects the patellar or Achilles tendon and can lead to enthesopathy or spontaneous tendon ruptures. 

13. Clinical picture Onset occurs in infancy & childhood Urine blackens on standing & diapers become stained Blackish spots in eyes, dorsum of hand, pinna + B rown macules on the sclera (Osler's sign). No intellectual deficits

14. Ochronotic pigments deposited in the bone impair the bone mineralization process and lead to osteopenia or osteoporosis.

15. T riad dark-colored urine , ochronosis , and ochronotic arthropathy

16. XRAYS Disc- elliptical, thin, calcified wafers Apposing vertebrae – sclerotic Large joints – degenerative changes +

17. Aspiration of the synovial effusion often reveals floating black particles, also called as the “ground pepper sign”

18. HPE - showed deposition of ochronotic pigment

19. Lab Diagnosis Diagnostic reaction – Bluish green coloration produced by addition of dilute ferric chloride solution to urine – FERRIC CHLORIDE TEST +VE Benedicts test + ve Urine becomes dark on standing when it becomes alkaline. Blackening is accelerated on exposure to sunlight & O2. Urine wen kept in a test tube will start to blacken from top layer Silver Nitrate test + ve

20. Rx Nitisonine ( reversible inhibitor 4- hydroxyl phenyl pruvate oxidase , an enzyme in tyrosine catabolic pathway)- 2mg once daily Reduce intake of food containing tyrosine & phenylalanine + administration of Vitamin C