Test Paper 1
Teck Yew Chin, Susan Cheng Shelmerdine, Akash Ganguly, Chinedum Anosike in Get Through, 2017
This is a typical description of CPPD, which can be idiopathic or associated with endocrinological problems such as hyperparathyroidism and hypothyroidism. The joints of the knee, wrist and second/third MCP joints of the hand are most frequently involved. Differentials would also include gout, but the distribution of erosions are different, with gouty erosions tending to be juxta-articular and punched out (‘rat-bitten’) rather than subchondral. Joint space is also typically preserved in gout until the late stages. Psoriasis produces enthesitis and periostitis with new bone formation. Ochronosis, or alkaptonuria, is a metabolic disorder whereby there is abnormal build-up of homogentisic acid in connective tissue with pigmentation of the sclera and urine appearing dark in colour. Diffuse multilevel vertebral disc calcification and early OA changes in multiple joints are associated with this condition.
Acne Scarring and Patients of African Descent
Antonella Tosti, Maria Pia De Padova, Gabriella Fabbrocini, Kenneth R. Beer in Acne Scars, 2018
Hydroquinone reduces the production of melanin by inhibiting tyrosinase, which is responsible for converting L-3,4-dihydroxyphenylalanine (DOPA) to melanin. Other mechanisms of action, including destruction of melanocytes, degradation of melanosomes, and inhibition of deoxyribose nucleic acid and ribonucleic acid synthesis, have been attributed to hydroquinone. It is available in over-the-counter concentrations of 1%–2%, with a prescription strength of 3%–4% and compounded at 5%–10%. It is recommended to begin treatment after the acne is under control, or even after 2–4 weeks of acne treatment and should be applied after application of topical acne medication. Treatment can be used as spot treatment or diffusely once to twice a day. Results may be noticed within 8–12 weeks [6]. Adverse effects include irritant and allergic dermatitis, temporary hypopigmentation of surrounding normal skin, giving a halo appearance, and the much-debated exogenous ochronosis with prolonged use. Instruction on how to apply the hydroquinone product over an entire cosmetic unit will help to avoid the localized halo side effect. Various formulations are available; some with additives such as glycolic acid, tretinoin, vitamin C, steroids, sunscreens, and microsponges enhance delivery and efficacy of hydroquinone [29].
Histopathology
Dimitris Rigopoulos, Alexander C. Katoulis in Hyperpigmentation, 2017
Inherited ochronosis (alkaptonuria) is caused by a defect in the enzyme homogentisic acid oxygenase, which inhibits the metabolism of homogentisic acid. Intermediates of homogentisic acid bind to collagen fibers of skin and cartilage. The skin shows gray or black macules and patches on the face, neck, and distal extremities. Bluish discoloration of the sclerae and of the cartilage of the ears, and sometimes of the nose, may also be present. Histopathologically, the fibers are orange, and in the skin they may fill the entire dermis (Figure 23.19).3,46
The potential of nitisinone for the treatment of alkaptonuria
Published in Expert Opinion on Orphan Drugs, 2019
There are still challenges and research to be done to understand the variability in the presentation of tyrosinemia and ocular pathologies associated with nitisinone administration in AKU patients, it is likely there are other variable factors within individuals that are responsible for these variations given that the dose of nitisinone administered in trials affects some but not others. The validation of Raman spectroscopy as a technique that has the ability to identify differing spectra of tissues with and without ochronosis is an exciting proposition particularly as it has already been validated as being able to detect pathological matrix in other osteoarticular tissues. This may prove useful for monitoring the absence/presence of ochronosis and enable the therapy to be targeted to an individuals presentation of ochronosis in tissues, given there is variability within an individual’s connective tissues (different tissues pigment at different rates) and across affected individuals. This may also mean that there is a reduced requirement for younger populations needing the administration of nitisinone, which still requires further research in AKU populations. AKU may also benefit from future advances in gene replacement or enzyme replacement therapies, only time will tell. The fact that this disease is the result of a single enzyme defect that causes an elevation in a single tyrosine metabolite suggests that it may be a useful model to look at gene therapies for more complex conditions where some of this information is yet to be clarified.
Inflammatory rheumatic diseases in patients with ochronotic arthropathy
Published in Modern Rheumatology, 2021
Tuba Yuce Inel, Pelin Teke Kisa, Ali Balci, Sadettin Uslu, Zumrut Arslan, Burcu Ozturk Hismi, Ulku Ucar, Nur Arslan, Fatos Onen, Ismail Sari
Alkaptonuria (AKU) is an autosomal recessive metabolic disease caused by mutations in the homogentisate 1, 2-dioxygenase (HGD) gene. The prevalence of AKU is rare, which is estimated at 1 in 250000 to 1000000 individuals [1]. The defect in the HGD enzyme leads to the accumulation of homogentisic acid (HGA) and its products in the connective tissues (ochronosis) [2]. Patients with ochronosis tend to be asymptomatic in early adulthood and become symptomatic during the second and third decades of life [2,3]. The involvement of the musculoskeletal (MSK) system, which is known as ochronotic arthropathy (OcA), mainly affects weight-bearing peripheral joints such as the knee and hip, spine, and soft tissues. Premature osteoarthritis, osteopenia, and fractures, rupture of the tendons, muscles, or ligaments due to the altered tissues could be seen in the course of the OcA [4,5].
Successful treatment of attention-deficit/hyperactivity disorder accompanying to alkaptonuria with methylphenidate and risperidone
Published in Psychiatry and Clinical Psychopharmacology, 2019
Alkaptonuria (AKU) is a metabolic disorder resulting from deficiency of homogentisic acid (HGA) oxidase that converts HGA (an intermediate product in of tyrosine metabolism) to maleylacetoacetate. This rare disorder is inherited in an autosomal recessive manner with an estimated prevalence of 1:250,000–1,000,000 individuals; however, the prevalence is unknown in the Turkish population. Clinically, it may manifest with dark discolouration of urine, ochronosis at cartilage and connective tissues, arthritis at third of fourth decade of life, cardiac valve deficits, crystalluria and/or renal stone disease, spontaneous tendon rupture, and involvement of liver, small intestine, and colon. In a recent study, it was reported that HGA oxidase gene was expressed in human cerebral tissue and neuronal cells in AKU with multi-systemic organ involvement. However, the dark discolouration of the urine sample is almost the only marker for early diagnosis [1–6]. It is unknown whether amyloid or HGA accumulation in alkaptonuria has an apparent effect on brain development. Also, it has been found that the disease has no effect on life expectancy [7]. To the best of our knowledge, there is no study or case report about psychiatric comorbidities in patients with AKU, although comorbid psychiatric disorders such as mental retardation, attention-deficit/hyperactivity disorder (ADHD), impulse control disorder, or conduct disorder can be seen in some metabolic diseases such as mucopolysaccharidosis (MPS), Wilson’s disease, or phenylketonuria (PKU) [8–10]. Here, we presented a paediatric AKU patient with comorbid ADHD, ODD/CD, and borderline intellectual functioning that was successfully treated with extended-release methylphenidate (OROS-MPH) and risperidone.
Related Knowledge Centers
- Alkaptonuria
- Dermatitis
- Connective Tissue
- Eardrum
- Hydroquinone
- Homogentisic Acid
- Tyndall Effect
- Phenol
- Coordination Complex
- Arthropathy