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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 Sep 2015Alkaptonuria is disorder of tyrosine metabolism due to deficiency of homogentisic oxidase characterized by excretion of homogentisic acid in urine, deposition of...
Alkaptonuria is disorder of tyrosine metabolism due to deficiency of homogentisic oxidase characterized by excretion of homogentisic acid in urine, deposition of oxidized homogensitate pigments in connective tissues and articular cartilages (ochronosis). The result is dark pigmentation and weakening of the tissues resulting in chronic inflammation and osteoarthritis. Management of alkaptonuric ochronic osteoarthritis is usually symptomatic and replacements have comparable outcomes to osteoarthritis in patients without ochronosis. I report a case of a patient with ochronosis of knee treated with total knee replacement and report operative pearls for surgery in this rare disorder.
PubMed: 28326376
DOI: 10.1016/j.artd.2015.03.003 -
Cureus Nov 2023Exogenous ochronosis (EO) results as a complication of long-term usage of skin lightening creams containing hydroquinone or other bleaching agents. Duration of use and...
Exogenous ochronosis (EO) results as a complication of long-term usage of skin lightening creams containing hydroquinone or other bleaching agents. Duration of use and concentration of hydroquinone in the product are noted to be key factors that decide the occurrence of EO. With more cases being reported globally, current classification systems lack practical applicability and may not be adequate for detecting early cases. Dermoscopy and clinicopathological correlation are very important for early diagnosis of EO to avoid undue overuse of hydroquinone leading to further deterioration of pigmentation. We report a series of six patients in one year with EO with the minimum duration of use of hydroquinone being three months to the development of ochronosis. The most common strength of hydroquinone used was 2%, documented in 5/6 cases. Three out of six patients (50%) had discordant findings according to the Dogliotti classification, while four out of six patients (66.7%) had discordant findings according to the Phillips classification. Our findings suggest that EO can occur with a shorter duration of hydroquinone use, even at lower percentage strengths. We propose that it may be more useful to accept the clinical presentation supported by dermoscopic features as adequate actionable findings, consider all the histopathological stages as warning signs of ochronosis or impending ochronosis, and terminate the use of hydroquinone in such patients.
PubMed: 38161945
DOI: 10.7759/cureus.49620 -
Actas Dermo-sifiliograficas May 2015
Topics: Facial Dermatoses; Female; Humans; Hydroquinones; Middle Aged; Ochronosis; Skin Lightening Preparations
PubMed: 25267567
DOI: 10.1016/j.ad.2014.06.015 -
Indian Journal of Ophthalmology Jun 2017Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of...
Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of homogentisic acid in connective tissues (ochronosis). Most common ocular manifestations are bluish-black discoloration of the conjunctiva, cornea, and sclera. In this case report, a 39-year-old Indian male patient with additional ocular features in the retina is described.
Topics: Adult; Alkaptonuria; Conjunctiva; Cornea; Diagnosis, Differential; Eye Diseases; Humans; Male; Ochronosis; Retina; Sclera; Tomography, Optical Coherence
PubMed: 28643719
DOI: 10.4103/ijo.IJO_337_16 -
Journal of Clinical Medicine Research May 2019Alkaptonuria (AKU) is a rare genetic disease associated with the deposition of melanin-like pigments (ochronosis) in connective tissues. However, data regarding the...
BACKGROUND
Alkaptonuria (AKU) is a rare genetic disease associated with the deposition of melanin-like pigments (ochronosis) in connective tissues. However, data regarding the effect of oxidative stress products on disease pathogenesis are limited. The purpose of this study was to investigate oxidative stress and related factors in patients with alkaptonuria and compare the findings with those in healthy control subjects.
METHODS
The study sample comprised of 21 AKU patients and 19 age- and sex-matched healthy controls. Serum samples were obtained to detect the total antioxidative capacity (TAC), and oxidation degradation products of thiobarbituric acid-reactive substances, protein carbonyls, advanced oxidation protein products, and homogentisic acid levels in urine were determined.
RESULTS
Serum TAC, oxidation degradation products of thiobarbituric acid-reactive substances, and protein carbonyl levels in the AKU group were higher than those measured for the control subjects, and the difference was statistically significant (P < 0.05). Moreover, a positive correlation was found between the patient's serum protein carbonyl, patient's age and AKU severity score (r = 0.492 and 0.746, respectively; P < 0.05). Furthermore, the protein carbonyl serum levels can be used to predict the disease severity score in alkaptonuria patients (P < 0.05).
CONCLUSIONS
In sum, the study results provide further support for the role of oxidation in the pathogenesis of alkaptonuria, suggesting presence of a more complex relationship than what has been previously assumed. Thus, further studies are needed to clarify these conflicting results.
PubMed: 31019628
DOI: 10.14740/jocmr3801 -
Journal of Medical Case Reports Oct 2022We present this report of a new ophthalmic finding in a patient with ochronosis.
BACKGROUND
We present this report of a new ophthalmic finding in a patient with ochronosis.
CASE PRESENTATION
An 85-year-old Caucasian male patient with bilateral dark temporal and nasal pigmentation of conjunctiva and sclera was referred to our hospital owing to low visual acuity. On biomicroscopic examination, bilateral horizontal Descemet's membrane folds were observed. Corneal tomography revealed irregular and asymmetric "against-the-rule" astigmatism in both eyes. Anterior segment optical coherence tomography demonstrated numerous central Descemet's without edema or other corneal structure alterations.
CONCLUSION
This is the first report of Descemet's membrane folds in ochronosis. These corneal findings suggest that the accumulation of homogentisic acid in the sclera leads to thickening and stiffness of this region. These alterations could remarkably decrease visual acuity owing to topographic corneal curvature alterations, especially in elderly patients.
Topics: Aged; Aged, 80 and over; Cornea; Descemet Membrane; Homogentisic Acid; Humans; Male; Ochronosis; Visual Acuity
PubMed: 36183119
DOI: 10.1186/s13256-022-03599-x -
Medical Journal, Armed Forces India Jul 2018A 60-year-old female presented with a 20-year history of progressive dark bluish discoloration of skin and passage of dark colored urine, painful arthritis and a recent...
A 60-year-old female presented with a 20-year history of progressive dark bluish discoloration of skin and passage of dark colored urine, painful arthritis and a recent history of invasive ductal carcinoma of right breast. Skin biopsy revealed hyaline material which was Periodic-Acid-Schiff stain positive and Congo-red stain negative, urine analysis revealed dark urine with presence reducing substance and radio-imaging showed intervertebral ossification and joint ankyloses. The patient was managed symptomatically with physiotherapy and acetaminophen on as required basis. This image is reported as a classic case of Alkaptonuria with clinical, histopathological and radio-imaging findings and the presence of invasive ductal breast carcinoma in the same patient.
PubMed: 30093780
DOI: 10.1016/j.mjafi.2017.06.009 -
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 -
European Journal of Rheumatology Sep 2018Exogenous ochronosis is characterized by hyperpigmented skin lesions that arise in association with local suppression of homogentisic acid oxidase enzyme. Although it...
Exogenous ochronosis is characterized by hyperpigmented skin lesions that arise in association with local suppression of homogentisic acid oxidase enzyme. Although it generally develops in association with topical application of chemical agents, it can occasionally develop in association with antimalarial drugs. Here we present the case of a patient with rheumatoid arthritis who developed hyperpigmentation on the face and neck regions during hydroxychloroquine treatment. Hydroxychloroquine is being widely used in rheumatology practice, and cutaneous hyperpigmentation may develop as an adverse effect. In the present case, we emphasize the potential underlying mechanisms through which it may cause cutaneous hyperpigmentation and determine the clinical and histopathological findings of exogenous ochronosis.
PubMed: 30071940
DOI: 10.5152/eurjrheum.2018.17190