Inflammatory rheumatic diseases in patients with ochronotic arthropathy.

BACKGROUND: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. METHODS: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed. RESULTS: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis (n = 1; 12.5%), interstitial lung disease (n = 1; 12.5%), and scleritis (n = 1; 12.5%), was also noted. CONCLUSION: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts.

[Severe spine lesion following alkaptonuria. Case report]. / Tyazheloe porazhenie pozvonochnika pri alkaptonurii. Opisanie klinicheskogo sluchaya.

Alkaptonuria is a rare autosomal recessive disease. In these patients, melanin-like compounds as the final products of impaired metabolism of homogentisic acid are deposited mainly in connective tissue, including cartilage tissue of intervertebral discs. Similar to other degenerative spine diseases, lumbar segment is often damaged. The authors report a 67-year-old patient with alkaptonuria. Compression of cauda equina by damaged cartilage masses of intervertebral discs and spine ligaments with deposits of ochronotic pigment is described. Previously diagnosed alkaptonuria in this patient was confirmed by surgical findings (black pigmentation) and histological data.

Collagen atomic scale molecular disorder in ochronotic cartilage from an alkaptonuria patient, observed by solid state NMR.

UNLABELLED: In pilot studies of the usefulness of solid state nuclear magnetic resonance spectroscopy in characterizing chemical and molecular structural effects of alkaptonuria on connective tissue, we have obtained (13) C spectra from articular cartilage from an AKU patient. An apparently normal anatomical location yielded a cross polarization magic angle spinning spectrum resembling literature spectra and dominated by collagen and glycosaminoglycan signals. All spectral linewidths from strongly pigmented ochronotic cartilage however were considerably increased relative to the control indicating a marked increase in collagen molecular disorder. This disordering of cartilage structural protein parallels, at the atomic level, the disordering revealed at higher length scales by microscopy. We also demonstrate that the abnormal spectra from ochronotic cartilage fit with the abnormality in the structure of collagen fibres at the ultrastructural level, whereby large ochronotic deposits appear to alter the structure of the collagen fibre by invasion and cross linking. SUMMARY: Increased signal linewidths in solid state NMR spectra of ochronotic articular cartilage from an AKU patient relative to linewidths in normal, control, cartilage reveals a marked decrease in collagen molecular order in the diseased tissue. This atomic level disordering parallels higher length scale disorder revealed by microscopic techniques.

Biochemical identification of homogentisic acid pigment in an ochronotic egyptian mummy.

Roentgenograms of an Egyptian mummy, dating from 1500 B.C., showed extensive calcification of the intervertebral discs and articular narrowing in both hip and knee joints. Biopsy cores from the right hip showed parallel black zones in the region of the articular surfaces, leading to a clinical diagnosis of ochrinosis. The black pigment was extracted, analyzed, and compared to an air-oxidized homogentistic acid polymer. The two substances apparently were identical. The chemical evidence thus confirms the clinical finding of ochronosis, an autosomal recessive disorder. This is, so far as known, the earliest verified case of this disorder.

Ochronosis Involvement and Extensity With 18F-FDG PET/CT.

Ochronosis (alkaptonuria) is an autosomal recessive inherited metabolic disease that causes pigmentation by accumulation of homogenous acid in the connective tissue. The most important causes of morbidity are ochronotic arthropathy and cardiovascular involvement seen in fourth and sixth decades, respectively. In this case report, we report the prevalence of F-FDG PET/BT findings in a 48-year-old man with ochronosis who underwent F-FDG PET/BT imaging for the evaluation of mediastinal lymphadenopathy.

"As Black as Ink": A Case of Alkaptonuria-Associated Myelopathy and a Review of the Literature.

STUDY DESIGN: Case report and literature review. OBJECTIVE: To characterize the rare presentation of myelopathy occurring secondary to alkaptonuria and to evaluate the available evidence regarding its treatment. SUMMARY OF BACKGROUND DATA: Alkaptonuria is an autosomal recessive genetic condition with an estimated incidence of 1 in 250,000 to 1 in 1,000,000 people. Mutation of the enzyme homogentisate 1,2-dioxygenase leads to the production of high levels of homogentisic acid, with subsequent deposition in ligaments, cartilage, and menisci. Involvement of the spine is termed "ochronotic spondyloarthropathy," of which myelopathy is an uncommon presentation. METHODS: We present the case of a 57-year-old man with alkaptonuria-associated myelopathy, who underwent surgical decompression. Ten additional cases were identified in the literature by a systematic search of PubMed and Google Scholar. RESULTS: In a patient presenting with myelopathy, alkaptonuria may be suspected because of medical history, family history, symptoms (including darkened urine, pigmented ear cartilage, and sclera), or radiographic changes, such as multilevel disc collapse, progressive wafer-like disc calcification, extensive osteophyte formation, and spinal deformity. The diagnosis can be confirmed by urine homogentisic acid testing. Of the 11 patients presented here or identified in the literature, 2 were treated nonoperatively, 8 were treated with decompressive spinal surgery, and treatment of the myelopathy was not discussed for 1 patient. In all cases in which outcomes were reported, substantial improvement in the patient's condition was seen. CONCLUSION: Alkaptonuria is a rare cause of myelopathy, but one that clinicians should understand. Although no disease-modifying treatment currently exists for alkaptonuria, the use of symptomatic treatments and, particularly, surgical decompression is recommended to address myelopathy if it develops. LEVEL OF EVIDENCE: 4.

Ochronosis in differential diagnosis of patients with chronic backache: a review of the literature.

A 50-year-old man presented with a complaint of low-back pain and widespread joint pain for the previous 20 years. Conventional radiography revealed wide areas of calcification in the intervertebral discs and degenerative changes in the peripheral joints. A diagnosis of ochronosis was made by the observation of bluish-brown pigmentation in the nose and ears, dark urine colors following alkalization, and high levels of homogentisic acid in the urine. Ochronosis should be considered in the differential diagnosis of patients with chronic low-back pain regarding features of widespread calcification in the intervertebral discs at radiography and bluish-brown pigmentation in the nose and ears.

Orthopaedic problems in patients affected by alkaptonuria. A case report.

Alkaptonuria is a rare congenital metabolic disorder. A defect of the enzyme homogentisic oxidase results in a block of the metabolic pathway of the amino acids phenylalanine and tyrosine. Deposits of homogentisic acid polymers in connective tissue cause various organ manifestations, including musculoskeletal symptomatology. A 66 year-old woman was twice admitted to our Department because of progressive knee and low back pain. Physical examination and accessory investigations confirmed that her various complaints were caused by underlying alkaptonuria. We use this case and a review of literature to discuss orthopaedic problems in patients with alkaptonuria and describe the cardinal signs and symptoms of this disease, its diagnosis and treatment.

Ochronotic arthropathy as a paradigm of metabolically induced degenerative joint disease. A case-based review.

Alkaptonuria is a rare, hereditary metabolic disorder in which a deficiency in the homogentisate 1,2-dioxygenase enzyme results in an accumulation of homogentisic acid. Deposition of excess homogentisic acid in different intra- and extra-articular structures with high content of connective tissue causes brownish-black pigmentation and weakening, ultimately resulting in tissue degeneration and finally osteoarthritis. Ochronotic arthropathy is considered a rapidly progressive, disabling condition in which weight-bearing joints and the thoracolumbar spine are predominantly affected. Patients often require multiple joint replacements, such as in the case of the patient presented here. At present, there is no definitive cure for ochronosis, and management is predominantly symptomatic.

Spontaneous tendon ruptures in alkaptonuria.

Ochronosis, the musculoskeletal manifestation of alkaptonuria, is known to lead to degenerative changes of the spine and weight-bearing joints. Symptoms related to degeneration of tendons or ligaments with spontaneous ruptures have not previously been reported. Three patients are described with four spontaneous ruptures of either the patellar tendon or tendo Achillis as the first symptom of alkaptonuria.

Ochronotic arthropathy: rapid destructive hip osteoarthritis associated with metabolic disease.

Ochronosis is a musculoskeletal manifestation of alkaptonuria, an inherited metabolic disorder associated with various systemic abnormalities related to the deposition of homogentisic acid pigment in connective tissues. This report describes a 58-year-old woman with ochronotic arthropathy who, in addition to the typical clinical features of the disorder, presented with rapidly progressive hip osteoarthritis. The destruction of the joint architecture and the severe functional impairment necessitated a total hip replacement which resulted in a satisfactory outcome.

Spinal abnormalities similar to ankylosing spondylitis in a 58-year-old woman with ochronosis.

Ochronotic arthropathy (spondylosis or peripheral arthropathy) is a late complication of alkaptonuria. There is a tendency for HLA-B27 positive patients with alkaptonuria to develop ochronotic spondylosis. A 58-year-old white woman, presented with ochronotic spondylosis. She was HLA-B27 positive. Her family history was positive for alkaptonuria. Ochronotic patients with HLA-B27 positivity develop spinal changes similar to ankylosing spondylitis (AS).

Bilateral hip arthroplasty for ochronotic arthropathy.

Ochronosis is a musculoskeletal manifestation of alkaptonuria, a rare hereditary metabolic disorder characterised by the absence of the enzyme homogentisic acid oxidase and associated with various systemic abnormalities related to the deposition of homogentisic acid pigment (ochronotic pigment). In this report, we describe a 53-year-old, HLA-B27(+) woman with ochronotic arthropathy. In addition to the typical clinical features of the disorder, she had bilateral hip involvement, which was improved by cementless total hip prosthesis.

Hereditary ochronosis: hyperpigmented skin overlying cartilaginous structures.

Hereditary ochronosis, or alkaptonuria, results from deficiency of homogentisic acid oxidase. It is an autosomal recessive condition found in geographically isolated populations. The excess homogentisic acid deposits in collagenous structures, leading to unusual pigmentation of the skin overlying cartilaginous structures, but on occasion pigment is also seen in the sclera, in sweat after oxidation, and classically, in urine when left standing at room temperature. This case report highlights the pathogenesis and expression of this rare disorder.

A case of alkaptonuria with root canal stenosis.

Spinal involvement in alkaptonuria is common. Patients usually present in the third or fourth decade with spondylosis or acute intervertebral disc prolapse. Alkaptonuria with root canal stenosis has however hitherto not been reported. We wish to report one such patient.