Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

JDD authors Deepika Narayanan, MD and Stephen K. Tyring, MD, PhD, MBA present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin- lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis; however, discontinuing the skin-lightening creams halted the progression of the patient’s skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. The authors summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.

Introduction

Exogenous ochronosis (EO) is a common skin condition that presents as asymptomatic hyperpigmentation after using products containing hydroquinone. Other causative agents include resorcinol, phenol, mercury, picric acid, and antimalarials such as quinine. Hydroquinone in concentrations above 4% and treatment courses as short as 3 months may be associated with EO.¹ We present the case of a patient with a classic history of hydroquinone use with contradicting biopsy findings.

Case Report

A 79-year-old Black woman presented with a 10-year history of blue-black macules and patches on the face. She had no notable medical history. Cutaneous examination revealed multiple blue-black macules and patches distributed symmetrically over the periorbital, malar, and forehead regions (Figure 1). The lesions were arranged in a reticular, lace-like pattern. No other sites were involved, and systemic examination was normal.

Further history revealed the patient had been using topical skin-lightening creams for years prior to the onset of her skin findings (Figure 2). The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Discontinuing the skin-lightening creams halted the progression of the patient’s skin lesions, supporting a diagnosis of EO.

A shave biopsy was performed and showed sparse superficial perivascular dermatitis with numerous melanophages, consistent with a diagnosis of lichen planus pigmentosus (LPP), confounding the final diagnosis. While the histopathologic findings did not show classic EO signs, the clinical diagnosis favors EO since the patient was using hydroquinone prior to the onset of the lesions, which in contrast can be used in the treatment of LPP. The biopsy findings may represent post-inflammatory hyperpigmentation from chronic lesions.

Discussion

EO is common in skin of color and Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these subgroups.² A recent study found hydroquinone-associated ochronosis was most often reported in middle-aged women of African descent, Black races, and Fitzpatrick skin types III to VI.¹ Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada.

Hydroquinone-associated EO was first described by Findlay in 1975.³ Clinically, it presents as blue-black or blue-gray hyperpigmented macules and patches arranged in a reticular, lace-like pattern. Dermoscopy can aid in the recognition of ochronosis, as the pigment appears blue-gray, appearing different from melasma and other forms of hyperpigmentation.² On histopathology, ochronosis characteristically presents as yellow-brown ochre “banana-shaped” fibers in the dermis. In advanced stages, there is a degeneration of the ochronotic fibers and the formation of a colloid milium.²

EO develops over three stages: initial erythema and mild dyspigmentation, followed by hyperpigmented black macules, and in severe cases, dark brown or black papules and nodules.⁴ Reversing the hyperpigmentation can be difficult. The first step in treatment is avoidance of hydroquinone-containing products to prevent the progression of the lesions. To reduce hyperpigmentation, topical retinoids, chemical peels, dermabrasion, and lasers have been reported in the literature with varying results.⁵ The majority of studies found no improvement with retinol, and in some cases worsening of hyperpigmentation.⁵ Low-potency corticosteroids had mixed efficacy, and complete resolution of hyperpigmentation has not been seen.⁵ Lasers used to treat EO include CO₂, Q-switched ruby, Q-switched alexandrite, Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG), intense pulsed light (IPL), and erbium-doped yttrium aluminum garnet (Er:YAG), and have shown promising results in many patients, but often require multiple treatment sessions to see an effect.⁵ However, in darker skin types, post-inflammatory hyperpigmentation is an important risk to consider. Cryotherapy, topical trichloroacetic acid, and the use of sunscreen alone have not been shown to improve pigmentation in EO.⁵

While the etiology by which hydroquinone causes EO is not fully certain, it is theorized that the inhibition of homogentisic acid oxidase enzyme activity results in homogentisic acid accumulation, which polymerizes to ochronotic pigmentation in the skin.⁶ Additionally, since the involvement of EO is often limited to the face and neck in photo-exposed regions, sun exposure may contribute to the process.⁵ Thus, sun protection should be advised to all patients with EO to prevent the progression of existing lesions.

EO can mimic other skin conditions, as seen in this case. LPP may mimic EO with gray-brown hyperpigmentation in sun-exposed areas in people with darker skin. LPP is often preceded by a pruritic phase which indicates activity and progression of disease. Furthermore, topical hydroquinone can be utilized as a treatment for LPP in conjunction with tacrolimus ointment. Melasma can appear similarly to OE on sun-exposed areas of the face and is also more common in women with darker skin types. Melasma clinically presents as tan, evenly pigmented macules symmetrically distributed on the face. However, pigment deposition is usually epidermal. On dermoscopy, melasma appears as a reticular pattern accentuation of normal pseudo-rete, dark-brown granules and globules with follicular sparing.⁴ Patients with melasma are often prescribed skin-lightening agents with hydroquinone, which may lead to the development of EO in patients with pre-existing melasma. Argyria presents as blue-gray discoloration of the skin, including mucosa and sclera, from the deposition of silver within the skin. Involvement of the mucosa and gingivae and associated neurological deficits may help differentiate argyria from EO.

Conclusion

This case highlights the challenge of differentiating EO from similar dermatoses but underscores the importance of making an accurate and early diagnosis to prevent the progression to more severe presentations with papules and nodules.

References

1. Levin CY, Maibach H. Exogenous ochronosis: an update on clinical features, causative agents and treatment options. Am J Clin Dermatol. 2001;2(4):213-217.
2. Ishack S, Lipner SR. Exogenous ochronosis associated with hydroquinone: a systematic review. Int J Dermatol. 2022;61(6):675-684.
3. Findlay GH, Morrison JG, Simson IW. Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol. 1975;93(6):613-622.
4. Dogliotti M, Leibowitz M. Granulomatous ochronosis: a cosmetic-induced skin disorder in blacks. S Afr Med J. 1979;56(19):757-760.
5. Simmons BJ, Griffith RD, Bray FN, et al. Exogenous ochronosis: a comprehensive review of the diagnosis, epidemiology, causes, and treatments. Am J Clin Dermatol. 2015;16:205-212.
6. Brenner M, Hearing VJ. Modifying skin pigmentation: approaches through intrinsic biochemistry and exogenous agents. Drug Discov Today Dis Mech. 2008;5(2):e189-e199.

Source

Narayanan, Deepika, and Stephen K. Tyring. “Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?.” Journal of Drugs in Dermatology: JDD 23.7 (2024): 567-568.

Content and images used with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

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