A tale of two disorders of hypopigmentation: The potential role of Cutibacterium acnes dysbiosis in progressive macular hypomelanosis and lichen striatus

By Warren R. Heymann, MD, FAAD
April 30, 2025
Vol. 7, No. 17

The human microbiome of the skin, gastrointestinal tract, and airways comprises distinct populations of bacteria, fungi, viruses, and mites and plays an essential role in homeostasis. The skin microbiome represents the totality of microbial genes within the community of skin microorganisms. The microbes are often considered commensal but may be symbiotic pathogenic. (1) The skin microbiome may be altered by external factors such as the environment or medications (notably antibiotics) and has been implicated in inflammatory (atopic dermatitis, psoriasis, seborrheic dermatitis, acne vulgaris, and hidradenitis suppurativa), neoplastic (Merkel cell carcinoma, Kaposi sarcoma), or other diseases. In 2018, I stated that “dysbiosis” would be the medical word to watch. (3) This editorial will focus on two entities with intriguing recent literature on how dysbiosis may be a factor in presenting with hypopigmentation — progressive macular hypomelanosis (PMH) and lichen striatus (LS).

C. acnes, formerly known as Propionibacterium acnes, was renamed in 2016. C. acnes is a lipophilic, anaerobic Gram-positive bacterium that colonizes human skin, predominantly residing in the sebum-rich pilosebaceous units of the face and upper trunk; it may also be detected in nonsebaceous areas. There are three subspecies of C. acnes with genetic and morphological differences: C. acnes subsp. acnes (phylotype I), C. acnes subsp. defendans (phylotype II), and C. acnes subsp. elongatum (phylotype III); a total of six main phylotypes (IA1, IA2, IB, IC, II, III) are distinguished. Colonization of human skin with multiple strains of C. acnes (predominantly phylotypes IA1, IB, and type II) increases during puberty. (4)

PMH is a common disorder. In my experience, patients are often misdiagnosed as tinea versicolor. Guillet et al. first described PMH in 1988. “Dermatological practice in Martinique frequently encounters a bizarre skin condition presenting as a progressive and extensive hypomelanosis on the back. The course of this disorder is highly characteristic: it occurs mainly in females from 18–25 years of age, with a progressive development of round, pale, coalescent macules on the back and sometimes on the abdomen. This disease, which does not respond to therapy, spontaneously regresses within 3 to 4 years. (5). Lichen striatus albus, seen in darker patients, presents with hypopigmented macules at the onset of disease. (6) Decreased epidermal melanin is the only histological feature. Ultrastructural examination of two cases found that the macular lesions were characterized by a switch from Stage IV single melanosomes (negroid) to small Type I-III aggregated melanosomes (caucasoid). It may thus be stated that the variation in skin coloration in these patients was due to a variation in melanosome size and distribution.” (5)

Westerhof et al. discovered follicular red fluorescence restricted to lesional skin in PMH patients, suspecting a relation with a porphyrin-producing bacteria residing in the sebum of the pilosebaceous duct. Biopsy specimens from the lesional skin of 8 women demonstrated gram-positive bacteria in the pilosebaceous duct accompanied by a mild perifollicular lymphocytic infiltrate. In all but one patient, Propionibacterium acnes was yielded from cultured biopsy specimens taken from follicular lesional skin. Healthy follicular skin did not show bacteria in histological sections, and cultures did not yield anaerobic bacteria, suggesting a relation between the presence of P. acnes and the hypopigmented macules. The authors proposed “that a factor is produced by these strains of P acnes, which interfere with melanogenesis. Based on these observations, we are undertaking a clinical trial to find a treatment for this troubling, intractable disease.” (7) If C. acnes play a crucial role in PMH, why are lesions mostly truncal? McDowell et al. explain: “More recent culture and metagenomic typing studies indicate that strains of C. acnes subsp. elongatum (type III) may be important in the aetiology of the condition, which would help to explain why PMH does not normally affect the face since such strains are rarely present there, and why no association between this condition and acne vulgaris is found.” (8) Although there is no definitive treatment for PMH, complete repigmentation was achieved with narrowband UVB phototherapy, benzoyl peroxide wash, and clindamycin lotion. (9)

LS is a benign, self-resolving, linear inflammatory dermatosis, most commonly affecting children aged 5–15 years. Females are affected approximately 2–3 times as often as males. LS characteristically presents as hypopigmented or erythematous papules corresponding to lines of Blaschko. Lesions typically involve the upper and lower limbs. (10) Nails may be affected — with or without cutaneous involvement — appearing thick, ridged, or split. Histologically, LS demonstrates a lichenoid and peri-eccrine infiltrate. (11)

Many patients have a history of atopy, and environmental triggers may be at play in the pathogenesis of LS. (10) LS has been reported after COVID-19 (12) and post-COVID-19 vaccination. (13) According to Rao et al., “The mosaic areas follow the lines of Blaschko, an embryonic migration pathway of keratinocyte precursors. The development of embryologically abnormal keratinocyte clones secondary to somatic mutations is thought to result in T-cell mediated inflammatory reactions when immune tolerance is lost. This theory is supported by histological findings of CD8+ T cells surrounding necrotic keratinocytes. Although the exact pathogenesis of hypopigmentation in LS is unknown, one proposed explanation ascribes pigment loss to transient disruption of the basal and supra-basal layers of the epidermis by inflammation, interfering with melanocyte and keratinocyte function. The resulting immunological destruction of melanocytes is thought to result in hypopigmentation.” (6)

In a fascinating study, Yu et al considered the role of dysbiosis in LS by comparing the microbiome (using whole genome sequencing) in LS patients without hypopigmentation (n=7) to LS patients with hypopigmentation (n=11). C. acnes was more significantly abundant in LS patients with hypopigmentation than in those with hypopigmentation. (C. acnes subsp. elongatum (type III) was not explicitly mentioned in this study). Malasseziarestricta was also abundant in the LS hypopigmentation group (M. furfur was not reported), suggesting that azelaic acid could be associated with LS hypopigmentation. The authors concluded that dysbiosis of the skin microbiome is associated with LS hypopigmentation. (14) Although LS is self-limited and usually treated with topical steroids or topical calcineurin inhibitors, these findings suggest that topical agents such as clindamycin or ketoconazole could prevent hypopigmentation in patients with LS.

In conclusion, we are in the infancy of comprehending how the human microbiome affects skin disease. The dictum that association does not equate with causation should always be kept in mind. Furthering our knowledge should lead to novel therapies for myriad disorders.

Point to Remember: The human (and skin) microbiome is intricately involved in health and disease. Recent studies suggest that dysbiosis may be pathogenic in disorders of hypopigmentation, such as progressive macular hypomelanosis and lichen striatus.

Our expert’s viewpoint

Hyunchang Ko, MD, PhD
Dermatologist, Professor
Department of Dermatology, School of Medicine, Pusan National University, South Korea

Can microorganisms cause non-infectious hypopigmented skin diseases?

Our skin and its symbiotic microorganisms maintain homeostasis and balance in healthy states. However, in certain pathological conditions, this balance can be disrupted, and the increase of specific microorganisms may be directly or indirectly related to disease causation. My dermatology mentor emphasized to colleagues that most skin diseases, even non-infectious conditions such as inflammatory or pigmentary skin disorders, are associated with microbial changes.

Thirty years ago, the methods available to prove these associations were limited to microscopic observations through biopsies and the culture or PCR of specific microorganisms. However, recent advancements in genetic information analysis techniques, including Next-Generation Sequencing (NGS), have progressed microbiome research and addressed these previous limitations.

Progressive macular hypomelanosis is a relatively common hypopigmented skin disorder found in young adults, and studies by Westerhof et al. have demonstrated the significant role of Propionibacterium acnes in the development of hypopigmented lesions. In clinical practice, when coral-red fluorescent spots are observed under Wood’s lamp, excellent treatment outcomes can be achieved through combination therapy with topical or systemic antibiotics and phototherapy.

Lichen striatus, a common inflammatory skin disease in children, is generally known for its self-limiting course. However, in individuals of color, hypopigmented lesions may persist for years after the resolution of inflammation, creating significant challenges. These hypopigmented areas can notably remain for extended periods without responding to specific treatments.

As noted by Dr. Heymann, recent studies utilizing microbiome analysis provide evidence linking specific microorganisms (such as bacteria or fungi) to non-infectious skin diseases. However, it remains unclear whether the increase in these specific bacteria is a precursor to skin disease or a consequence of subsequent changes, suggesting that further in-depth research is needed to clarify these relationships.

1. MacGibeny MA, Adjei S, Pyle H, Bunick CG, Ghannoum M, Grada A, Harris-Tryon T, Tyring SK, Kong HH. The Human Skin Microbiome in Health: CME Part 1. J Am Acad Dermatol. 2024 Aug 19:S0190-9622(24)02671-9. doi: 10.1016/j.jaad.2024.07.1498. Epub ahead of print. PMID: 39168311.

2. MacGibeny MA, Adjei S, Pyle H, Bunick CG, Ghannoum M, Grada A, Harris-Tryon T, Tyring SK, Kong HH. Alterations in the Skin Microbiome in Dermatologic Diseases and with External Exposures: CME Part 2. J Am Acad Dermatol. 2024 Aug 20:S0190-9622(24)02672-0. doi: 10.1016/j.jaad.2024.07.1499. Epub ahead of print. PMID: 39173885.

3. Heymann WR. The medical word to watch in 2018: Dysbiosis. Dermatology World Insights and Inquiries. January 4, 2018. https://staging.aad.org/dw/dw-insights-and-inquiries/dermatopathology/the-medical-word-to-watch-in-2018-dysbiosis

4. Ahle CM, Feidenhansl C, Brüggemann H. Cutibacterium acnes. Trends Microbiol. 2023 Apr;31(4):419-420. doi: 10.1016/j.tim.2022.10.006. Epub 2022 Oct 31. PMID: 36328874.

5. Guillet G, Helenon R, Gauthier Y, Surleve-Bazeille JE, Plantin P, Sassolas B. Progressive macular hypomelanosis of the trunk: primary acquired hypopigmentation. J Cutan Pathol. 1988 Oct;15(5):286-9. doi: 10.1111/j.1600-0560.1988.tb00561.x. PMID: 3209765.

6. Rao M, Young K, Jackson-Cowan L, Kourosh A, Theodosakis N. Post-Inflammatory Hypopigmentation: Review of the Etiology, Clinical Manifestations, and Treatment Options. J Clin Med. 2023 Feb 3;12(3):1243. doi: 10.3390/jcm12031243. PMID: 36769891; PMCID: PMC9917556.

7. Westerhof W, Relyveld GN, Kingswijk MM, de Man P, Menke HE. Propionibacterium acnes and the Pathogenesis of Progressive Macular Hypomelanosis. Arch Dermatol. 2004;140(2):210–214. doi:10.1001/archderm.140.2.210

8. McDowell A, McLaughlin J, Layton AM. Is Cutibacterium (previously Propionibacterium) acnes a potential pathogenic factor in the aetiology of the skin disease progressive macular hypomelanosis? J Eur Acad Dermatol Venereol. 2021 Feb;35(2):338-344. doi: 10.1111/jdv.16789. Epub 2020 Jul 20. PMID: 32603510.

9. Leonard N, Krueger S, Rashighi M. Successful treatment of progressive macular hypomelanosis. Dermatol Reports. 2020 Oct 22;12(2):8509. doi: 10.4081/dr.2020.8509. PMID: 33408831; PMCID: PMC7772758.

10. Mendiratta V, Meena AK. Clinical and epidemiological profile of lichen striatus in children-Experience from a tertiary care hospital. Pediatr Dermatol. 2023 Jul-Aug;40(4):642-643. doi: 10.1111/pde.15345. Epub 2023 Jun 8. PMID: 37290834.

11. Charifa A, Jamil RT, Ramphul K. Lichen Striatus. 2023 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29939607.

12. Herzum A, Viglizzo G, Gariazzo L, Ferro J, Vellone VG, Occella C. Lichen striatus after COVID-19. Clin Dermatol. 2022 Nov-Dec;40(6):744-746. doi: 10.1016/j.clindermatol.2022.09.006. Epub 2022 Oct 4. PMID: 36202381; PMCID: PMC9529674.

13. Belina ME, Sarver MM, Al-Rohil R, Fresco A. Lichen striatus post-COVID-19 vaccination. JAAD Case Rep. 2021 Oct;16:16-18. doi: 10.1016/j.jdcr.2021.07.031. Epub 2021 Aug 18. PMID: 34423105; PMCID: PMC8372434.

14. Yu Y, Lee B, Shin K, Kim K, Lee HJ, Shin JO, Lee J, Kim HS, Kim BS, Kim MB, Kim YH, Ko HC. Association between the skin microbiome and lichen striatus hypopigmentation: Cutibacterium acnes as a potential cause. J Eur Acad Dermatol Venereol. 2024 Sep;38(9):1776-1782. doi: 10.1111/jdv.19746. Epub 2024 Jan 3. PMID: 38173132.

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