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.

Hyperpigmentation: Looking beyond hydroquinone.

Hyperpigmentation is the most common complaint in the age group 40-45 years, seeking consultation for skin disorders. Hydroquinone is a commonly used depigmenting agent in clinical practice for treating hyperpigmentation. Prolonged use of hydroquinone has been associated with cancer risk and exogenous ochronosis. The CARES (The Coronavirus Aid, Relief, and Economic Security Act) Act of 2020 has instituted significant changes to hydroquinone containing OTC (over the counter) products, and consequently, many hydroquinone-based OTC products had to be withdrawn from the market. Henceforth, products containing hydroquinone would need US Food and Drug Administration approval via new drug application pathways for commercialization. Alternative treatment options to hydroquinone in clinical practice are reviewed in this paper with regard to their safety and efficacy vis a vis hydroquinone. Also, new potential treatment options such as thiamidol, Polypodium leucotomos, and glutathione are discussed. The review shows that these alternative depigmenting agents can be rationally combined to achieve desired treatment goals in the management of hyperpigmentation.

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.

Exogenous ochronosis associated with hydroquinone: a systematic review.

Exogenous ochronosis is a potential side effect associated with hydroquinone, and treatment is often unsatisfactory. Our study objectives were to review data on hydroquinone-associated ochronosis to determine risk factors for patients experiencing this adverse event. On September 27, 2020 (MEDLINE/PubMed), and October 30, 2020 (Scopus and Web of Science), databases were searched for "ochronosis + hydroquinone" by both authors to reduce risk basis. PRISMA reporting guidelines were used to select 56 articles with a total of 126 patients with hydroquinone-associated ochronosis. Included articles described hydroquinone-associated ochronosis. Articles were excluded if they had irrelevant content, were non-English language text, and were non-case studies. Full text articles were assessed and recorded. Cross-tabulation analysis was performed on categorical data, and Fisher exact test was performed. Ochronosis was most often reported in middle-aged women (53.2%), of African descent (45.2%), Black races (55.5%), and Fitzpatrick skin types V-VI (52.4%). It was most frequently reported with unknown and hydroquinone concentrations greater than 4% (32.5 and 35.7% cases, respectively). Median duration of use was 5 years, with only four cases reported with courses 3 months or shorter and eight cases reported with use 1 year or less. All patients presented with facial blue-black or gray-blue macules in a reticulate, lace-like fashion. Histopathology consistently showed solar elastosis and brownish-yellow, 'banana-shaped' fibers between degenerated collagen fibers of the papillary dermis. Based on these findings, we conclude that hydroquinone in concentrations above 4% and in treatment courses longer than 3 months may be associated with new-onset ochronosis.

Hydroquinone: myths and reality.

Hydroquinone has pharmacological uses in disorders of pigmentation because of its ability to competitively inhibit the enzyme tyrosinase. Our contemporary review presents the strongest evidence supporting the use of hydroquinone with the most effective and tolerable formulations combining hydroquinone, retinoid and corticosteroid (modified Kligman formula or 'triple combination cream'). The risk of exogenous ochronosis is low if prescribed concentrations of ≤ 5 for a limited period with regular monitoring. Dermatologists should reassure patients that with controlled use, hydroquinone can be well-tolerated and safe for a range of hyperpigmentary conditions.

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.

Corneal and Scleral Problems Caused by Skin-Lightening Creams.

PURPOSE: To present a case series of patients with corneal and scleral changes associated with the use of skin-lightening creams. This is the first report of corneal changes with these widely available creams. METHODS: Three patients of West African origin presented with strikingly similar skin, corneal, and scleral changes and were found to have all been using skin-lightening creams containing hydroquinone. Histopathology was obtained for 1 patient. RESULTS: Three patients were referred to the corneal clinics of 2 hospitals with corneal changes and a history of blurred vision for 1 to 3 years. There was a 60-year-old woman from Nigeria and a 68-year-old woman and a 73-year-old man both from Ghana. All 3 had been using skin-lightening lotions containing hydroquinone on their faces for between 3 and 15 years and had black-blue facial pigmentation of exogenous ochronosis, a recognized complication of these creams. Their corneas all had horizontal striae radiating across the posterior corneas with scleral thinning and plaques. Linear brown epithelial pigmentation was observed within the lower third of the corneas. Biopsy of the sclera in 1 patient showed ochronosis. CONCLUSIONS: We present previously unreported eye changes associated with the use of skin-lightening creams containing hydroquinone, with a triad of signs: posterior corneal striae radiating from 3 o'clock to 9 o'clock, thinning and plaques in the sclera, and a normal endothelial cell count. Similar pathological changes are seen in exogenous ochronosis, a recognized skin complication of hydroquinone, are seen in the sclera.

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.

Use of skin-lightening products among selected urban communities in Accra, Ghana.

BACKGROUND: The practice of skin lightening has been reported from North America, Europe, Asia, and Africa. In literature, some prevalence rates exceed 50%, and both sexes are involved. Common agents used include hydroquinone, mercury, corticosteroids, and caustic agents. The agents are easily accessible and affordable with very little regulation. Cutaneous and systemic side effects occur but do not appear to be a deterrent, as the notion of light skin as a surrogate for beauty is strong. In Ghana, anecdotal reports of high bleaching rates among certain urban communities resulted in a study supported by the Food and Drugs Authority to determine various facets of this practice. METHODS: A cross-sectional study among adults in selected urban fishing communities of Accra was undertaken. Consecutive cases were enrolled after written informed consent. A questionnaire was administered, followed by physical examination and clinical photographs. Descriptive statistics were used to analyze the data. RESULTS: Of the 555 participants from the three communities, prevalence was 279 (50.3%). Duration of use ranged from 2 months to 17 years. Approximately 212 (76%) used more than one product, and 231 (82%) used agents on their face and body. Dermatological features were hypopigmentation 270 (96.8%), other color changes including ochronosis 241 (86.4%), changes in consistency 141 (50.3%), striae 157 (56.3%), and infections 42 (15.1%). CONCLUSIONS: The prevalence of skin bleaching was 50.3% in these communities, which is high considering the adverse effects from the practice. We recommend regulation of products by enforcing the law, more education, and a population prevalence study.

A role for interleukins in ochronosis in a chondrocyte in vitro model of alkaptonuria.

Alkaptonuria is a rare autosomal recessive condition resulting from inability to breakdown homogentisic acid (HGA), an intermediate in tyrosine degradation. The condition has a triad of clinical features, the most damaging of which is ochronotic osteoarthropathy. HGA is elevated from birth, but pigmentation takes many years. We hypothesise that interleukins play a role in initiation and progression of ochronotic osteoarthropathy. C20/A4 cells were cultured and maintained in 9-cm petri dishes containing either HGA at 0.33 mM, a single interleukin (IL-1ß, IL-6 or IL-10) at 1 ng/ml or a combination of HGA and a single interleukin. Statistical analysis of pigment deposits and cell viability was performed using analysis of variance with Newman-Keuls post-test. All cultures containing HGA showed a significant increase in pigment deposition compared to control and IL cultures alone. The cultures containing HGA and IL-6 showed a significant increase in pigment deposits compared to HGA alone. The cell viability counts across all cultures on day 10 demonstrated a significant decrease in cultures containing HGA compared to those which did not. There was no significant difference between cultures containing just HGA or those combined with an interleukin. This work demonstrates a role for cytokines present in the joint(s) in the pigmentation process, particularly IL-6, and that the presence of HGA in joint tissues appears more detrimental to chondrocytes than the presence of any of the interleukins found in response to joint injury, trauma and osteoarthritis (OA). This further supports the evidence that the arthropathy in alkaptonuria is much more severe and rapidly progressing.