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Autopsy & Case Reports Sep 2020Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive...
Exogenous Ochronosis (EO): Skin lightening cream causing rare caviar-like lesion with banana-like pigments; review of literature and histological comparison with endogenous counterpart.
Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive disorder with deficiency of the enzyme homogentisic acid oxidase), or exogenously in patients using phenol products such as topical creams containing hydroquinone or the intramuscular application of antimalarial drugs. Exogenous ochronosis (EO) typically affects the face and was reported in patients with dark skin such as Black South Africans or Hispanics who use skin-lightening products containing hydroquinone for extended periods. Recently more cases have been reported worldwide even in patients with lighter skin tones, to include Eastern Indians, Asians, and Europeans. However, just 39 cases of EO have been reported in the US literature from 1983 to 2020. Here we present two cases; a 69 and a 45-year-old female who were seen for melasma, given hydroquinone 4% cream daily and tretinoin 0.05%. Both patients noticed brown spots on their cheeks, which progressively enlarged and darkened in color. The diagnosis of ochronosis was confirmed by characteristic histopathological features on the punch biopsy. Unfortunately, neither patient responded to multiple treatments (to include, tazarotene 0.1% gel and pimecrolimus ointment, topical corticosteroids, and avoidance of hydroquinone containing products). We also present a case of classic (endogenous) ochronosis in a patient with alkaptonuria to picture the histological similarities of these two entities. EO is an important clinical consideration because early diagnosis and treatment may offer the best outcome for this notoriously refractory clinical diagnosis.
PubMed: 33344320
DOI: 10.4322/acr.2020.197 -
Calcified Tissue International Feb 2021Alkaptonuria (AKU) is characterised by increased circulating homogentisic acid and deposition of ochronotic pigment in collagen-rich connective tissues (ochronosis),...
Alkaptonuria (AKU) is characterised by increased circulating homogentisic acid and deposition of ochronotic pigment in collagen-rich connective tissues (ochronosis), stiffening the tissue. This process over many years leads to a painful and severe osteoarthropathy, particularly affecting the cartilage of the spine and large weight bearing joints. Evidence in human AKU tissue suggests that pigment binds to collagen. The exposed collagen hypothesis suggests that collagen is initially protected from ochronosis, and that ageing and mechanical loading causes loss of protective molecules, allowing pigment binding. Schmorl's staining has previously demonstrated knee joint ochronosis in AKU mice. This study documents more comprehensively the anatomical distribution of ochronosis in two AKU mouse models (BALB/c Hgd, Hgd tm1a), using Schmorl's staining. Progression of knee joint pigmentation with age in the two AKU mouse models was comparable. Within the knee, hip, shoulder, elbow and wrist joints, pigmentation was associated with chondrons of calcified cartilage. Pigmented chondrons were identified in calcified endplates of intervertebral discs and the calcified knee joint meniscus, suggesting that calcified tissues are more susceptible to pigmentation. There were significantly more pigmented chondrons in lumbar versus tail intervertebral disc endplates (p = 0.002) and clusters of pigmented chondrons were observed at the insertions of ligaments and tendons. These observations suggest that loading/strain may be associated with increased pigmentation but needs further experimental investigation. The calcified cartilage may be the first joint tissue to acquire matrix damage, most likely to collagen, through normal ageing and physiological loading, as it is the first to become susceptible to pigmentation.
Topics: Alkaptonuria; Animals; Cartilage; Chondrocytes; Female; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Ochronosis; Pigmentation
PubMed: 33057760
DOI: 10.1007/s00223-020-00764-6 -
Orthopedic Reviews Jun 2020Patients with alkaptonuria can present ochronotic degenerative arthropathy due to the accumulation of pigments in the cartilages. Ochronotic arthropathy initially...
Patients with alkaptonuria can present ochronotic degenerative arthropathy due to the accumulation of pigments in the cartilages. Ochronotic arthropathy initially affects the spine, then there is the involvement of the other large joints, with greater frequency of the knees. In this article we will present two patients with alkaptonuria who have been effectively treated with knee and hip replacement, comparing our experience with what is available in the literature.
PubMed: 32913615
DOI: 10.4081/or.2020.8687 -
The American Journal of Case Reports Sep 2020BACKGROUND Alkaptonuria (AKU) is a rare metabolic disease caused by a deficiency in homogentisic acid oxidase, which leads to the accumulation of homogentisic acid dark...
BACKGROUND Alkaptonuria (AKU) is a rare metabolic disease caused by a deficiency in homogentisic acid oxidase, which leads to the accumulation of homogentisic acid dark pigments in tissues such as bones, ligaments, and tendons. Long-term duration of this condition, termed ochronosis, can result in degenerative arthropathy involving the spine and large joints. CASE REPORT This report describes a 55-year-old Jordanian woman presenting with chronic neck and lower back pain. History, physical examination, and radiological imaging indicated cervical myelopathy and lumbar spine degeneration. Two-level anterior cervical discectomy and fusion was performed successfully. Intra-operatively, the cervical discs were observed to be black, suggesting a diagnosis of alkaptonuria, which was later confirmed by genetic testing. A detailed history and physical examination revealed the absence of classical features of AKU. CONCLUSIONS Intraoperative detection of black disc material suggests the need for further tests to diagnose AKU, especially in indolent patients who did not have classical clinical features. Surgical management may improve outcomes in patients with cervical myelopathy due to ochronosis.
Topics: Alkaptonuria; Diskectomy; Female; Humans; Low Back Pain; Middle Aged; Ochronosis; Spinal Cord Diseases
PubMed: 32908119
DOI: 10.12659/AJCR.924575 -
JIMD Reports Sep 2020Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression.
BACKGROUND
Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression.
METHODS
Photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at V-1 (pre-baseline visit), V0 (baseline visit when 2 mg nitisinone was commenced), and yearly at V1, V2, and V3 visits. Photographs were inspected for evolution of ochronotic pigment and also scored categorically to derive eye, ear, and combined ochronosis scores. An ear cartilage biopsy was also carried out at V0 and one year after V3 (V4) and ochronotic pigment was assessed and quantitated. Visits were compared for changes in pigment. Fasting blood and 24-hour urine samples were collected for measurement of HGA.
RESULTS
There were 80 AKU patients at V0, and 52, 47, and 40 at V1, V2, and V3 in the group with variable numbers (VAR Group) respectively; 23 patients attended once before V0, in the V-1 visit. Photographs of patients show increase in eye pigment between V-1 and V0, followed by decrease post-nitisinone at V1, V2, and V3. Ear and combined ochronosis semiquantitative scoring showed an increase between V-1 and V0 ( < .01), followed by a decrease at V1, V2, and V3, in the VAR group ( < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease ( < .05).
CONCLUSIONS
Nitisinone decreases HGA and partially reverses ochronosis.
PubMed: 32904992
DOI: 10.1002/jmd2.12137 -
Arthroplasty Today Dec 2020Alkaptonuria is a rare autosomal recessive metabolic disorder. It is characterized by the accumulation of homogentisic acid in the body due to a lack of enzymes that...
Alkaptonuria is a rare autosomal recessive metabolic disorder. It is characterized by the accumulation of homogentisic acid in the body due to a lack of enzymes that degrade it. Over time, it results in joint degeneration and eventually leads to ochronosis. Ochronosis refers to bluish-black discoloration of connective and other tissues within the body. In this study, we present 5 distinct cases diagnosed with alkaptonuria. They have undergone 8 total joint replacement surgeries (4 hips and 4 knees) within 8 years (2010-2018). All patients had an excellent outcome over several years. The follow-up period ranged from 2 to 10 years. Although none of the presented cases had intraoperative or postoperative adverse sequelae, we must take care when dealing with patients with ochronotic arthropathy. They carry a higher risk of complications than other patients with osteoarthritis disease. These complications include fractures due to fragile bone quality, muscle or tendon rupture, joint instability, and anesthesia-related complications. Total joint arthroplasty is a valid and safe option in the management of hip and knee ochronotic arthropathy.
PubMed: 32875021
DOI: 10.1016/j.artd.2020.07.037 -
Arthroplasty Today Jun 2020Alkaptonuria is a rare metabolic disorder caused by the deficiency of homogentisic acid oxidase enzyme, which is responsible for eliminating homogentisic acid from the...
Alkaptonuria is a rare metabolic disorder caused by the deficiency of homogentisic acid oxidase enzyme, which is responsible for eliminating homogentisic acid from the body through the renal system. Excessive accumulation of homogentisic acid leads to ochronosis and ochronotic arthritis. Owing to the rarity of the disease, long-term functional outcomes of joint replacements of the hips and knees in ochronosis arthropathy are unconfirmed, and only a limited number of case reports are available on this. We present a case of a 45-year-old man with ochronosis and advanced osteoarthritis of both the hips and knees. He underwent bilateral hip and knee replacements as staged procedures. At a follow-up of more than 12 years, the man had full mobility with no loosening of implants.
PubMed: 32577465
DOI: 10.1016/j.artd.2020.01.012 -
International Journal of Surgery Case... 2020Alkaptunurea is a rare metabolic disorder with autosomal recessive genetic pattern in transmission, it is characterized by accumulation of hemogenistic acid in the...
INTRODUCTION
Alkaptunurea is a rare metabolic disorder with autosomal recessive genetic pattern in transmission, it is characterized by accumulation of hemogenistic acid in the tissues due to deficiency of homogentisate 1,2 dioxygenase activity. Characteristically, affected patient will have dark urine and blackish discoloration of connective tissue, especially cartilage and bone and hence it is known as black bone disease.
PRESENTATION OF THE CASE
The reported case is for 49 years old gentleman, known to have hypertension, hypothyroidism and Alkaptunurea. He presented to our facility with long standing bilateral knee pain (more in the left) with difficulty in doing daily activities. He presented to our tertiary facility after failure of previous treatment measures. The patient underwent uncomplicated Robotic assisted total knee arthroplasty that resulted in significant improvement of his pain and function.
CONCLUSION
Knee arthroplasty is a reliable and reproducible modality in treating Ochronotic knee arthropathy and it would result in pain reduction and better function of patients with such condition.
PubMed: 32554281
DOI: 10.1016/j.ijscr.2020.06.005 -
SAGE Open Medical Case Reports 2020Alkaptonuria is a rare autosomal-recessive metabolic disorder of tyrosine degradation which results in elevated levels of circulating homogentisic acid. Ochronosis...
Alkaptonuria is a rare autosomal-recessive metabolic disorder of tyrosine degradation which results in elevated levels of circulating homogentisic acid. Ochronosis occurs when homogentisic acid polymerizes and deposits in connective tissue. Ochronotic lesions in the carotid arteries have not been described. In this report, we describe a 65-year-old man with alkaptonuria, with hypertension and hyperlipidemia, who underwent an uneventful carotid endarterectomy for an asymptomatic high-grade internal carotid artery stenosis. Histology revealed homogentisic acid deposits as black-brownish areas in the intima. He was noted to have an impressive heavily brown-black pigmented discoloration of the carotid plaque. Cardiovascular involvement is a rare consequence of alkaptonuria and is manifested by pigment deposition at the areas influenced by shear stress and turbulence.
PubMed: 32284865
DOI: 10.1177/2050313X20915411 -
Angewandte Chemie (International Ed. in... Jul 2020Alkaptonuria (AKU) is a rare disease characterized by high levels of homogentisic acid (HGA); patients suffer from tissue ochronosis: dark brown pigmentation, especially...
Alkaptonuria (AKU) is a rare disease characterized by high levels of homogentisic acid (HGA); patients suffer from tissue ochronosis: dark brown pigmentation, especially of joint cartilage, leading to severe early osteoarthropathy. No molecular mechanism links elevated HGA to ochronosis; the pigment's chemical identity is still not known, nor how it induces joint cartilage degradation. Here we give key insight on HGA-derived pigment composition and collagen disruption in AKU cartilage. Synthetic pigment and pigmented human cartilage tissue both showed hydroquinone-resembling NMR signals. EPR spectroscopy showed that the synthetic pigment contains radicals. Moreover, we observed intrastrand disruption of collagen triple helix in pigmented AKU human cartilage, and in cartilage from patients with osteoarthritis. We propose that collagen degradation can occur via transient glycyl radicals, the formation of which is enhanced in AKU due to the redox environment generated by pigmentation.
Topics: Alkaptonuria; Cartilage, Articular; Electron Spin Resonance Spectroscopy; Homogentisic Acid; Humans; Magnetic Resonance Spectroscopy; Osteoarthritis; Oxidation-Reduction; Pigmentation; Pigments, Biological
PubMed: 32219972
DOI: 10.1002/anie.202000618