Appreciating the role of kojic acid in a case of exogenous ochronosis following melasma |
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Appreciating the role of kojic acid in a case of exogenous ochronosis following melasma

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Abstract

Exogenous ochronosis presents as a persistent grayish blue speckled hyperpigmentation on the sun exposed areas and bony prominences in the early stages. On progression, characteristic hyperpigmented caviar-like papules and rarely nodules are formed with speckled confetti like depigmentation. It can occur due to various causes, of which hydroquinone (HQ) usage for prolonged period is a common one. It is important to detect ochronosis in the early stages as further use of HQ will lead to worsening of pigmentation. A rare case is presented with exogenous ochronosis in a male patient following prolonged unsupervised use of HQ for melasma. He was eventually treated with kojic acid which not only helped in improving the condition but was also well-tolerated by the patient.

Case report

A 45-year-old Indian male, Fitzpatricks skin type V, working in an office desk job presented with extensive hyperpigmentation of the face since the last 10 years. He developed patchy facial hyperpigmentation on the cheeks, forehead and nose 12 years back following excessive sun exposure. This gradually progressed and he was diagnosed with melasma and prescribed a triple combination cream containing 2% HQ, 0.1% mometasone and 0.05% tretinoin. He developed redness and dryness following application so the cream was stopped. He then started applying topical HQ 2% cream on the advice of the local pharmacist and continued to apply it unsupervised for 8 years. There was an initial improvement in the first six months, followed by gradual worsening of the pigmentation.

On clinical examination, grayish brown to bluish black macules were present diffusely on the forehead, cheeks and nose. These were interspersed with confetti like hypopigmented macules on the malar region (Figure 1a, b). There were pinpoint, dark brown papules interspersed, which were more appreciable on palpation. On dermoscopy, there was an accentuation of the normal pseudonetwork of the facial skin with grayish brown dark amorphous structures in the perifollicular region with some obliteration of the follicular openings. Curvilinear and worm like dark brown to bluish deposits were seen (Figure 2). A biopsy revealed short, stout, curvilinear, banana-shaped, ochre-colored fibers of varying thickness in the papillary dermis (Figure 3). There was evidence of solar elastosis. Also, a few white dots were seen, which perhaps represented the confetti-like depigmentation. A diagnosis of exogenous ochronosis was made. He was treated with topical sunscreens and retinoic acid 0.025% and glycolic acid 6% followed by chemical peeling with 20% salicylic acid and 15% trichloroacetic acid (TCA) which provided mild benefit. He was then prescribed a cream containing 5% kojic acid and vitamin C for 4 weeks. As the treatment helped in improving the condition and was well-tolerated by the patient, it was continued for another 8 weeks. At follow-up visit, significant change was reported by the patient.

Discussion

Melasma is difficult to treat and requires prolonged treatment with skin lightening agents to maintain remissions. HQ is the most common agent used but can cause side effects such as skin irritation, phototoxic reactions, secondary post-inflammatory hyperpigmentation, depigmentation, and rarely ochronosis that can be irreversible.1-3 Ochronosis is clinically characterized by bluish black discoloration of the skin. It occurs due to accumulation of homogentisic acid (HGA) in the connective tissues. Broadly ochronosis is of two types; endogenous and exogenous. Endogenous ochronosis is an inherited disease that occurs due to deficiency of homogentisic acid oxidase (HGAO) enzyme and causes brown, black, or blue hyperpigmentation of the skin due to accumulation of HGA in the liver and irreversible binding of dermal fibrillar collagen tissue. Exogenous ochronosis (EO) is most commonly caused by prolonged topical therapy with HQ which inhibits the local activity of HGAO enzyme and leads to HGA accumulation that polymerizes to form ochronotic pigment. Other causes are resorcinol, phenol, mercury, picric acid and rarely also with systemic antimalarials.4-7,9

EO can be staged by severity, initially described by Dogliotti and Leibowitz. Stage I consists of erythema and mild pigmentation of the face and neck; stage II is a progression to hyperpigmentation, black colloid milia, and atrophy with the appearance of ‘caviar-like’ papules; and stage III includes papulonodules with or without surrounding inflammation.4 Dermoscopy can be a useful screening test and also help in selection of the biopsy site. As reported in some studies, the dermoscopic features of ochronosis include the presence of irregular, brown-gray, globular, annular, and arciform structures, with obliteration of some follicular openings.8,9 Berman et al10 reported dark brown globules and globular-like structures on a diffuse brown background in patients having EO, which was distinct from melasma that presents as a fine brown pseudoreticular pattern on a background of a faint light brown structure less area.10 The diagnosis is confirmed by biopsy, which shows the presence of distinct yellow brown banana shaped fibres in the dermis, often co-existing with solar elastosis.11 Melanophages may be seen in the upper dermis.12

It is usually very refractory to treatment and leads to psychological distress because of the dark pigmentation. The first step is stopping the offending agent. Sun protection is essential. Topical retinoic acid along with photoprotection may be beneficial in some cases. Mild topical steroids have been tried. Antioxidants such as vitamin C and vitamin E have also been used. Chemical peeling with glycolic acid or tricarboxylic acid and dermabrasion has shown benefit. Another promising treatment has been the long-term use of non-HQ and non-steroid depigmented preparations like kojic acid and glycolic acid. The following section highlights the effectiveness of kojic acid in individuals with hyperpigmentation.4,7,11,13

An insight into the role of kojic acid in management of hyperpigmentation

Kojic acid (5-hydroxy-2-hydroxymethyl-4-pyrone), a metabolic product of the fungal species Acetobacter, Aspergillus, and Penicillium acts by inhibiting the production of free tyrosinase. Moreover, it exhibits antioxidant properties. Information available from various studies have mentioned the efficacy of kojic acid, as monotherapy as well as in combination with other agents. In addition, it may be a viable therapeutic approach in patients who have difficulty in tolerating other first-line therapies.3,14,15

A 12-week randomized, single-center, single-blinded, parallel-group study involving 80 individuals with melasma compared the efficacy of kojic acid alone with either 2% HQ or 0.1% betamethasone valerate, and a combination of all these three agents. The results demonstrated that kojic acid along with HQ was superior in depigmenting in comparison to other three groups.15Another study that assessed whether the addition of kojic acid in a gel containing 10% glycolic acid and 2% HQ will improve melasma further showed that the side on which kojic acid was applied did better.3

Conclusion

When prescribing HQ, patients should be warned against prolonged usage and it should be used for short intermittent periods. Alternate skin lightening agents like kojic acid have better safety profile and should be used when prolonged therapy with skin lightening agents is required in cases such as melasma.

References

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  11. Martins VM, Sousa AR, Nde CP, et al. Exogenous ochronosis: Case report and literature review. An Bras Dermatol. 2012;87:633-6.
  12. Patel AB, Kubba R, Kubba A. Clinicopathological correlation of acquired hyperpigmentary disorders. IJDVL. 2013;79(3):367-375.
  13. Diven DG, Smith EB, Pupo RA, et al. Hydroquinone-induced localized exogenous ochronosis treated with dermabrasion and CO2 laser. J DermatolSurgOncol. 1990;16:1018-22.
  14. Bandyopadhyay D. Topical treatment of melasma. Indian J Dermatol. 2009;54(4):303–309.
  15. Hollinger JC, Angra K, Halder RM. Are Natural Ingredients Effective in the Management of Hyperpigmentation? A Systematic Review. J ClinAesthetDermatol. 2018;11(2):28–37.
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