Exogenous Ochronosis With Ocular Involvement From Chronic Use of Teavigo.

Exogenous ochronosis refers to accumulation of homogentisic acid metabolites in tissues, manifesting as pigmentation of affected tissues. Phenolic compounds are most commonly implicated, including hydroquinone, quinine, phenol, resorcinol, mercury, and picric acid. The affected connective tissues exhibit brownish discoloration when heavily pigmented and the histopathological appearance is characteristic with "banana-shaped" ochre-colored pigment deposits. Herein, the authors describe a rare case of exogenous ochronosis involving the conjunctiva, sclera and skin, as a result of chronic use of Teavigo (94% epigallocatechin gallate), a polyphenol compound with postulated antioxidant and antiapoptotic activity.

Dogliotti and Phillips classifications are unsuitable for grading the histopathological findings of exogenous ochronosis.

BACKGROUND: Cutaneous exogenous ochronosis (EO) is frequently graded and staged according to the Dogliotti or Phillips classification system, both in research studies and in clinical practice. There are no data to support the use of these systems in either of these settings. These systems additionally purport that the clinical and histopathological findings of EO are concordant; however, anecdotal evidence suggests otherwise. We aimed to determine the clinical-histopathological concordance rates in EO and to assess the suitability of the Dogliotti and Phillips classification systems for the grading and staging of EO lesions. METHODS: Five cutaneous EO cases diagnosed at our institution were studied. Clinical and histopathological data were obtained by medical record and histopathology slide review. Each case was assigned a clinical and histopathological grade according to both the Dogliotti and Phillips classifications. Clinical-histopathological concordance rates were determined for each classification. RESULTS: Clinical-histopathological concordance was seen in 80% and 60% of EO lesions when graded according to the Dogliotti and Phillips classifications, respectively. CONCLUSIONS: Cutaneous EO lesions do not consistently show clinical-histopathological concordance. Although the Dogliotti and Phillips classifications may have clinical utility, they are not suitable to grade EO histopathologically.

Occupational Localized Cutaneous Argyria With Pseudo-Ochronosis in a Jeweler.

ABSTRACT: A case of localized argyria in a 36-year-old female jeweler is described who presented with 2 discrete and asymptomatic bluish-black pigmented macules on the pulp of her left middle finger. A skin biopsy from both lesions demonstrated deposition of brown/black pigmented granules along the basement membrane zone of eccrine glands, blood vessels, nerves, and the dermo-epidermal junction fully in keeping with silver deposition. In addition, there was yellow-brown deposition seen within the interstitial dermis mimicking an early form of ochronosis, so called "pseudo-ochronosis." This latter feature is rarely described in cases of argyria. Transmission electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of electron dense particles up to 150 nm in diameter and the presence of silver, respectively. On further questioning, the patient had a history of localized and chronic exposure to silver, which specifically involved holding and manipulating silver wires and rings over the left middle finger. This case highlights an unusual and rare presentation of localized argyria in a jeweler. In addition, our case showed preferential silver deposition on dermal elastic fibers which has not been previously described in the literature.

Anatomical Distribution of Ochronotic Pigment in Alkaptonuric Mice is Associated with Calcified Cartilage Chondrocytes at Osteochondral Interfaces.

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.

Exogenous Ochronosis as an Elastotic Disease: A Light-Microscopic Approach.

BACKGROUND: Exogenous ochronosis (EO) is a deposition disease associated with application of hydroquinone-containing preparations. Characteristic ochronotic bodies (OBs) arise from endogenous connective tissues, most often reported as collagen. We highlight a significant role for elastic fibers as a precursor tissue. OBJECTIVE: To evaluate elastic tissue pathology in EO, specifically as it relates a precursor role in ochronotic body formation. METHODS: In this retrospective observational study, a literature review using PubMed/MEDLINE database was conducted to ascertain the most commonly ascribed precursor connective tissue. Eleven histopathologic cases of EO were identified. Patient demographics and clinical characteristics were recorded. Slides were reviewed for the presence and grade of solar elastosis (SE), the relationship of OBs to elastotic material, the presence of elastotic fibers transitioning to OBs, and positivity of bodies with Verhoeff-van Gieson elastic tissue stain. RESULTS: Elastic fibers are uncommonly reported as the major precursor tissue of OBs. SE was uniformly present in our cases, and the majority demonstrated heavy/high-grade elastosis. Elastotic fibers transitioning to OBs were observed in all cases, and the bodies demonstrated Verhoeff-van Gieson positivity. LIMITATIONS: Small sample size. CONCLUSIONS: Ochronotic body formation is associated with SE, and bodies appear to arise from damaged elastic fibers.

[Surgery in the dark - a case of Cardiac Ochronosis]. / Cirurgia no Escuro ­ Um Caso de Ocronose Cardíaca.

Alkaptonuria is a rare genetic disorder related to tyrosine metabolism. The cardiovascular manifestations are rare being the aortic stenosis the most commonly reported. We present a case of 72-year-old women who underwent aortic valve replacement with intraoperative findings in the aortic valve and the aortic wall suggestive of Cardiac Ochronosis. Once it is a rare disease there are issues related to the natural history of the disorder that still unknown, namely the type of aortic prothesis in use. For this reason, we find essential the documentation and follow-up of all these rare cases.

A Alcaptonúria é uma doença genética rara, relacionada com o metabolismo da tirosina. As manifestações cardiovasculares são a forma de apresentação menos comum da doença, sendo a estenose aórtica a patologia mais frequentemente encontrada. No presente artigo, apresentamos o caso de uma doente do sexo feminino de 72 anos proposta para cirurgia eletiva de substituição valvular aórtica com alterações intraoperatórias sugestivas de Ocronose Cardíaca. Atendendo à raridade da doença, muito há por esclarecer acerca da sua história natural, nomeadamente no que se refere ao tipo de próteses utilizadas, motivo pelo qual é essencial a documentação e seguimento destes casos.

Alkaptonuria: Spontaneous Achilles tendon rupture: Case report.

Alkaptonuria is an autosomal recessive disease caused by the accumulation of homogentisic acid (HGA) products in the ligament, cartilage, skin and various organs due to the lack of HGA oxidase enzyme. In this article, we present a 61-year-old male patient operated on due to a diagnosis of spontaneous Achilles tendon rupture and diagnosed as alkaptonuria due to the intraoperative color of the tissues and the subsequent examinations. We also reviewed alkaptonuria and its accompanying pathologies in light of the literature.

Unsafe Deposits: Overlapping Cutaneous Manifestations of Porphyria Cutanea Tarda, Ochronosis, Hemochromatosis, and Argyria.

Cutaneous deposition disorders represent an array of conditions resulting from the accumulation of endogenous and exogenous substances within the skin. Many of the deposition diseases resemble each other and can also be confused with disorders not related to deposition. Porphyria cutanea tarda (PCT) results from dysfunction particularly in the fifth enzyme of the heme synthesis pathway, leading to increased skin fragility and bullae among other abnormalities. Ochronosis develops from alkaptonuria or exogenous sources, creating deposition of ocher-colored pigment in the skin. Hemochromatosis is a systemic disorder that can be inherited or acquired, altering skin pigmentation in more than 90% of patients. PCT can be an initial manifestation of hemochromatosis. Argyria is an acquired disorder of silver deposition that can also cause pigmentation similar to ochronosis. These uncommon but not rare disorders may resemble and be confused with each other in multiple ways.

[Black knee-ochronotic alterations in alkaptonuria]. / Das schwarze Knie ­ ochronotische Veränderungen im Rahmen einer Alkaptonurie.

This article presents the case of a 53-year-old male patient born in Sri Lanka, who presented to the outpatient unit with the suspicion of empyema of the knee joint. Within the framework of knee arthroscopy, the diagnosis of ochronosis was made and later confirmed by histopathological biopsy. The alkaptonuria is caused by a homogentisate 1,2-dioxygenase deficiency and leads to an accumulation of homogentisic acid, a degradation product of tyrosine. This leads to the characteristic appearance of ochronosis with bluish-black deposits in the tissue (e.g. in connective tissue, sclera and ear cartilage) and a black coloration of the urine.

Ochronotic pigmentation is caused by homogentisic acid and is the key event in alkaptonuria leading to the destructive consequences of the disease-A review.

Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)-derived pigment in tissues altering the properties of these tissues, leading to their failure. Some tissues like cartilage are more easily affected by ochronosis while others such as the liver and brain are unaffected for reasons that are still not understood. In vitro and mouse models of ochronosis have confirmed the dose relationships between HGA and ochronosis and also their modulation by p-hydroxyphenylpyruvate dioxygenase inhibition. Ochronosis cannot be fully reversed and is a key factor in influencing treatment decisions. Earlier detection of ochronosis preferably by noninvasive means is desirable. A cause-effect relationship between HGA and ochronosis is discussed. The similarity in AKU and familial hypercholesterolaemia is explored and lessons learnt. More research is needed to more fully understand the crucial nature of ochronosis.

Exogenous ochronosis: the failure of depigmenting creams.

Exogenous ochronosis (EO) is an entity that manifests as black-bluish or grayish-brown cutaneous hyperpigmentation, which is a consequence of the deposition of ochronotic pigment with characteristic banana-like morphology between the collagen fibers of the dermis. Both the clinical presentation and histopathology appearance are superimposable with endogenous ochronosis or alcaptonuria, a hereditary disease in which ochronotic pigment deposition occurs at a multisystemic level. The most frequent cause of EO is the use of facial depigmenting creams containing hydroquinone, a common practice among women with high phototypes. We present a woman who developed EO on the face, upper chest, and back after prolonged use of a depigmenting cream containing hydroquinone.

Raman Spectroscopy identifies differences in ochronotic and non-ochronotic cartilage; a potential novel technique for monitoring ochronosis.

OBJECTIVE: Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine metabolism, where patients are unable to breakdown homogentisic acid (HGA), which increases systemically over time. It presents with a clinical triad of features; HGA in urine, ochronosis of collagenous tissues, and the subsequent ochronotic arthritis of these tissues. In recent years the advance in the understanding of the disease and the potential treatment of the disorder looks promising with the data on the efficacy of nitisinone. However, there are limited methods for the detection and monitoring of ochronosis in vivo, or for treatment monitoring. The study aim was to test the hypothesis that Raman spectra would identify a distinct chemical fingerprint for the non-ochronotic, compared to ochronotic cartilage. DESIGN: Ochronotic and non-ochronotic cartilage from human hips and ears were analysed using Raman spectroscopy. RESULTS: Non-ochronotic cartilage spectra were similar and reproducible and typical of normal articular cartilage. Conversely, the ochronotic cartilage samples were highly fluorescent and displayed limited or no discernible Raman peaks in the spectra, in stark contrast to their non-ochronotic pairs. Interestingly, a novel peak was observed associated with the polymer of HGA in the ochronotic cartilage that was confirmed by analysis of pigment derived from synthetic HGA. CONCLUSION: This technique reveals novel data on the chemical differences in ochronotic compared with non-ochronotic cartilage, these differences are detectable by a technique that is already generating in vivo data and demonstrates the first possible procedure to monitor the progression of ochronosis in tissues of patients with AKU.

The Dark Side of the Heart: Cardiovascular Manifestation of Ochronosis.

Alkaptonuria is rare genetic disorder of tyrosine metabolism manifesting with signs of tissue pigmentation, dark urine, and ochronotic arthropathies. Commonly undiscovered by late adulthood, alkaptonuria can manifest as cardiac ochronosis with cardiovascular disorders such as valvulopathies, but rarely coronary artery disease. This case report describes 2 patients with aortic stenosis and coronary artery disease in whom alkaptonuria was diagnosed during open heart surgery.