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Diagnosis: (Exogenous) Ochronosis.



Discussion:

There are two types of ochronosis: 1) endogenous ochronosis also known as alkaptonuria, which is inherited as an autosomal recessive trait, and 2) localized exogenous ochronosis, which is caused by the topical application of hydroquinone-containing creams to the exposed parts of the skin. These are usually applied in order to lighten the color of darker skin. Clinically, dark brown to black patches are seen, but in severe cases the areas may become macular blue and actually be associated with blue to black papules, milia, and nodules, and scars can occur. Endogenous ochronosis (alkaptonuria) results in the lack in the homogentisic acid oxidase. Homogentisic acid accumulates over the course of many years and in many tissues, especially in cartilages of the joints, the ears, and the nose, and in the ligaments and tendons, and in the sclerae. These can produce osteoarthritis; blackening of the cartilage, ligaments, and tendons; and patchy pigmentation of the sclerae. In the course of time, homogentisic acid accumulates in the dermis in sufficient amounts to cause patchy brown pigmentation in the skin that can be generalized. Currently, the gene for homogentisic acid oxidase maps to chromosome 3.

Essentially, localized endogenous ochronosis mimics the endogenous pattern because the topically applied hydroquinone inhibits the activity of homogentisic acid oxidase in the skin, resulting in the local accumulation of homogentisic acid, which polymerizes to form ochronotic pigments. In effect, this process mimics the cutaneous manifestations of endogenous ochronosis. Somehow, in an unknown mechanism, these ochronotic pigments affect the collagen and imbue themselves between the collagen fibers and can also cause localized collagen degeneration. Histologically, these ochronotic pigments are crescent shaped and brown, producing a telltale sign in this patient. A cutaneous biopsy was performed, and the skin sample demonstrated the findings of classic localized endogenous ochronosis.

This is a condition that I see in many of my patients. In some cultures and countries, particularly in African countires, skin lightening has been a custom and tradition handed down over time where many of the patients mistakenly think that making their skin lighter makes them more attractive. There are many preparations available to produce skin lightening. Many contain dangerous and harmful chemicals including arsenic and mercury. I also see patients using hydroquinone containing agents both over-the-counter and prescription strength for extended periods of time. Localized exogenous ochronosis can occur when hydroquinone-containing agents are used without supervision for lengthy periods of time. Therefore, I rarely recommend my patients use any topical hydroquinone-containing agent for more than four to six months. At that point, I always recommend a six-month vacation to avoid exogenous ochronosis. Hydroquinone containing agents are very helpful, and there has been lots of discussion recently with the FDA regulating their use and, currently, a potential ban on hydroquinone containing products. I personally believe they can serve a great benefit to our patients if used with supervision and proper education and instruction and the ban is ill-advised. The American Academy of Dermatology also opposes banning hydroquinone containing agents.

Dr. Kligman, generally regarded as the grandfather of Retin-A, and his resident dermatologist Dr. Willis many years ago came up what is known as the Willis-Kligman formula, a combination of hydroquinone (prescriptionength 4%), Retin-A, and mild hydrocortisone. This combination of three agents has been used by dermatologists for many years to lighten areas of hyperpigmentation. Hydroquinone itself is a bleaching agent for melanin, Retin-A also has lightening effects for melanin, hyperpigmentation also potentiates effects of hydroquinone, and because the two tend to be somewhat irritating, hydrocortisone is used mollify the irritating effects of the other two. This combination is now available in commercial prescriptionength preparations. The problem with treating melasma and other areas of hyperpigmentation in the skin is that oftentimes color/pigment can be deposited both high and low within the skin. Topical lightening creams and preparations can only penetrate so far. If the patient has pigment that is deposited deep in the skin, topical agents just cannot penetrate far enough to produce an acceptable result. That is why I tell most of my patients treating both melasma and hyperpigmentation, that satisfactory results are achieved approximately 50% of the time under the best of conditions. I explain to them how they may be genetically determined to produce color both high and low, resulting in only partial bleaching. Also, I always warn them about using any hydroquinone-containing product for more than four to six months to prevent the development of exogenous ochronosis, a situation that is exactly the opposite of what they are trying to achieve. Another topical agent that I use is kojic acid. This too has lightening effects, although not as strong as hydroquinone, but oftentimes I will cycle patients back and forth, alternating every four months to prevent exogenous ochronosis if they are achieving slow but continued improvement.




To read CME article on Skin Lightening and Depigmenting Agents



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