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 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 1  |  Issue : 2  |  Page : 52-55

Progressive macular hypomelanosis: An update


1 Department of Dermatology, University of Texas Southwestern Medical Center, Dallas; Innovative Dermatology, Plano, Texas, USA
2 Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, USA

Date of Web Publication15-Dec-2014

Correspondence Address:
Seemal R Desai
Clinical Assistant Professor, Department of Dermatology, Univ of Texas Southwestern Medical Center, Innovative Dermatology, 5425 W. Spring Creek Pkwy, Ste 265, Plano, TX, 75024
USA
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Source of Support: Seemal R. Desai, MD is a consultant and investigator for Galderma, AbbVie and Valeant., Conflict of Interest: None


DOI: 10.4103/2349-5847.147040

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  Abstract 

Progressive macular hypomelanosis (PMH) is a common and often misdiagnosed disorder characterized by numerous nummular, coalescing hypopigmented macules on the trunk of adolescents, and young adults. It was originally described in patients with Fitzpatrick skin types V-VI from tropical countries, but is now understood to have a worldwide distribution in a variety of skin types. The pathogenesis of PMH is unknown, but is thought to involve Propionibacterium acnes, which has been found in abundance in the pilosebaceous units of lesional skin. Biopsies of lesions demonstrate normal architecture of epidermis and dermis, but exhibit decreased melanin content. It is important to note that this is different from vitiligo, which has a total absence of melanin. Many patients with PMH often times go misdiagnosed for tinea (pityriasis) versicolor, postinflammatory hypopigmentation, and other dyschromias. Topical antifungal and corticosteroid therapy have proven ineffective in PMH, but successes have been reported with topical and systemic antibacterial treatment modalities and even phototherapy. Given the increasing prevalence of patients with skin of color, it is important to better understand the nature of this condition, along with its diagnosis, management, and treatment.

Keywords: Dyschromia, progressive macular hypomelanosis, Propionibacterium acnes, tropical countries


How to cite this article:
Desai SR, Owen JL. Progressive macular hypomelanosis: An update. Pigment Int 2014;1:52-5

How to cite this URL:
Desai SR, Owen JL. Progressive macular hypomelanosis: An update. Pigment Int [serial online] 2014 [cited 2019 May 21];1:52-5. Available from: http://www.pigmentinternational.com/text.asp?2014/1/2/52/147040


  Introduction Top


Progressive macular hypomelanosis (PMH) is a likely underdiagnosed, common disorder of dyschromia worldwide. It was first described in 1980s by Guillet et al. [1] in a population of mixed race (Negroid and Caucasoid) adolescents and young adults from Martinique. Other authors from around the world have applied their own terms for the condition: "Cutis trunci variata" in Venezuela, [2] "creole dyschromia" in the French West Indies, [3] "nummular and confluent hypomelanosis of the trunk" in The Netherlands, [4] and "idiopathic multiple large macule hypomelanosis" in the United States. [5] While PMH has been reported in a variety of fashions, as noted above, it is only a fairly recently recognized cutaneous dilemma.


  Clinical Presentation Top


The classical clinical presentation of PMH is asymptomatic, ill-defined, nummular, nonscaly, symmetric hypopigmented macules that coalesce into patches. [6] The lesions are distributed among areas of high sebaceous gland density, most commonly the lumbar and abdominal regions [Figure 1]. Occasionally lesions have been observed to progress to involve the neck and proximal extremities, but never the hands and rarely the face. PMH was originally described in Fitzpatrick skin types V-VI from tropical and subtropical areas, but has since been diagnosed worldwide in a variety of skin types. [7],[8],[9],[10] The vast majority of studies have reported a female predominance of about 3:1 or greater, [6],[7],[8],[9],[10],[11],[12] but not all studies have confirmed this. [2],[13] PMH is also primarily seen in adolescents and young adults, with the average age in the mid-20's. [6]
Figure 1: Progressive macular hypomelanosis. Clinical photographs (a) Before and (b) After 1 month topical 10% benzoyl peroxide treatment

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  Light and Electron Microscopy Top


Histologic differences between lesional and nonlesional skin are subtle. Both the epidermis and dermis are morphologically normal, with normal numbers of melanocytes. However, lesional skin had decreased melanin content compared to nonlesional skin. [7],[13] Ultrastructural analysis of lesional and nonlesional skin failed to show any difference in melanosome transfer or degradation. However, especially in Fitzpatrick skin type V-VI skin biopsies, there were increased numbers of small, aggregated Stages I-III transferred melanosomes, as opposed to the larger, single Stage IV transferred melanosomes observed in nonlesional skin. [14] This alteration in size and maturation of melanosomes was present, but less prominent in less melanized skin types. [13],[14] This might implicate altered the melanosome maturation in the pathogenesis of PMH.


  Pathogenesis Top


The exact etiology and pathogenesis of PMH is unknown. A serendipitous observation was made by Westerhof et al. [7] when they discovered hair follicles in PMH lesions fluoresce coral red under Wood lamp, but not interfollicular or non-lesional skin. This indicated the presence of a porphyrin-producing organism in the follicle, which they were able to isolate and identify as the Gram-positive, nonspore-forming, anaerobic rod Propionibacterium acnes. The isolated P. acnes were sensitive to penicillins, erythromycin, and clindamycin, but not metronidazole. No spores, hyphae, or other bacteria were isolated.

Propionibacterium acnes reside in the infundibular segment of the pilosebaceous unit, supporting both the distribution of clinical PMH lesions (high concentrations of sebaceous glands on trunk) and the restricted age distribution (adolescent to young adults with high sebum production). P. acnes have a pathogenic role in acne, but acne does not predispose a patient for PMH and acne is not more prevalent or worse in patients with PMH. One possible explanation for this discrepancy is that acne and PMH might be caused by different strains of P. acnes. [15] Amplified fragment length polymorphism for the 16S rRNA gene of P. acnes was used to determine if differences existed between P. acnes isolated from patients with acne versus PMH. In a majority of the PMH cases (8 out of 14), P. acnes bacteria were substantially different from the patients with acne. [15] Others have used real-time polymerase chain reaction to quantitatively show the number of genomic copies of P. acnes is significantly greater in lesional compared to nonlesional skin. [8] One possible role of P. acnes in the pathogenesis of PMH is the production of a putative depigmenting factor that would interfere locally with melanogenesis. [7] The presumed target would be an alteration in melanosome maturation and distribution. [13],[14]

Alternative PMH etiologies include hormonal, given the high female to male ratios observed in patient cohorts. [6],[7],[8],[9],[10],[11],[12] There is one case report where a patient who was 2 months pregnant had a sudden eruption of PMH. [16] Another etiology might include postinflammatory hypopigmentation secondary to an as yet undetermined factor. This is less likely given that in a study of 45 patients with PMH treated with benzoyl peroxide/clindamycin/ultraviolet (UVA) light versus fluticasone/UVA light, the antibacterial regimen was superior to the anti-inflammatory regimen. [17]


  Differential Diagnosis Top


Progressive macular hypomelanosis is not an uncommon disorder, and it is speculated that PMH is often misdiagnosed. [6] Other common conditions that mimic PMH include tinea (pityriasis) versicolor and pityriasis alba [Table 1]. Compared to these conditions, PMH lacks fine scale and is nonpruritic. Fungal cultures and potassium hydroxide preparation of PMH lesions are negative. PMH lesions do not respond to either antifungal or anti-inflammatory treatment. Partially treated or early vitiligo might be included in the differential but would not exhibit red follicular fluorescence under Wood lamp and is not associated with P. acnes. Idiopathic guttate hypomelanosis is another possibility, but it exhibits a photodistribution of small discrete macules in middle-aged and older adults as opposed to truncal coalescing macules in adolescents and young adults with PMH. Postinflammatory hypopigmentation would have a history of preceding or current dermatosis (e.g. tinea versicolor, pityriasis rosea) and would not exhibit progression as has been seen in PMH. Hypopigmented mycosis fungoides is another entity that should be ruled out, but might exhibit atrophy and textural changes that are absent in PMH. In endemic areas, tuberculoid or borderline tuberculoid leprosy, post kala-azar dermal leishmaniasis, and pinta should be considered in the differential diagnosis of PMH.
Table 1: Differential diagnosis for PMH

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  Treatment Top


It is important to recognize that there is no widely accepted first-line treatment for PMH. Given the putative bacterial etiology of the disease, it is not surprising that topical and systemic antifungals and topical corticosteroids have been unsuccessful treatments. [6] However, trials of antimicrobial therapy have largely been effective, and remain a mainstay of treatment today. As mentioned previously, a randomized within-patient left-right comparison study of 5% benzoyl peroxide hydrogel/1% clindamycin lotion/UVA irradiation versus 0.05% fluticasone cream/UVA irradiation in patients with PMH was performed. [17] Combination of benzoyl peroxide and clindamycin was chosen based upon studies in acne showing improved results and decreased development of drug-resistant P. acnes strains. [18] After 14 weeks treatment, significantly more repigmentation occurred on the antimicrobial treated sided compared to the anti-inflammatory treated side, and this difference persisted after 12 weeks follow-up without treatment. The UVA phototherapy was felt to speed repigmentation, but not directly treat the underlying disease. [17] A randomized, double-blind, placebo-controlled study of 23 patients with PMH was performed to assess the efficacy of topical combination 5% benzoyl peroxide and 1% clindamycin with sun exposure to placebo and sun exposure. [12] At the conclusion of 3 months, the antimicrobial group had significantly greater clinical improvement compared to placebo. The rate or time to relapse of PMH was not assessed. Some authors have had success with 2-3 months course of oral tetracyclines (doxycycline or minocycline 100 mg twice daily) and recommend this in combination with topical benzoyl peroxide and/or clindamycin. [11]

Phototherapy alone has been attempted for the treatment of PMH with variable results. Psoralen plus UVA (PUVA) therapy induced repigmentation after 6 weeks, but hypopigmented spots recurred in the same location within a few weeks after PUVA cessation. [19] An uncontrolled prospective study of narrowband-UVB (NB-UVB) therapy was performed on 17 patients with PMH. [10] The majority of patients experienced at least 90% repigmentation and 13 out of 17 experienced at least 50% repigmentation. After 6 months cessation of NB-UVB therapy, five of the 13 patients had a recurrence of hypopigmented patches. Repigmentation during NB-UVB treatment occurred by gradual darkening of lesions. This is in contrast to repigmentation observed in vitiligo that occurs from discrete perifollicular islands. Putative mechanisms for the efficacy of NB-UVB phototherapy include stimulation of melanogenesis and antimicrobial effects. [10],[20]

More recently a case was reported of successful treatment of PMH with oral isotretinoin. [21] The patient had both PMH and rosacea and was initially treated with NB-UVB for PMH without success. Subsequently 10 mg daily oral isotretinoin was prescribed for the patient's rosacea, which the patient stopped after 1 month because the PMH lesions resolved. The lesions had not recurred at the 10 months follow-up after stopping isotretinoin. One of the mechanisms isotretinoin treats acne is through the reduction of sebum production in the pilosebaceous unit where P. acnes reside. This might explain the outcome from this case, as a resultant decrease in P. acnes should allow for repigmentation.


  Conclusion Top


Progressive macular hypomelanosis is a common disorder seen globally in a variety of skin types. It is an under-recognized and often misdiagnosed clinical entity that is embarrassing and frustrating for patients who have been prescribed many futile treatments, including antifungals and corticosteroids. Several of the initial publications on the subject were not in English, which might have contributed to its lack of recognition. The pathogenesis is currently being elucidated, but an important step was the identification of P. acnes in the pilosebaceous units of lesional skin. Further work is needed to demonstrate how P. acnes are responsible for the depigmentation seen clinically. This will aid in the development of novel and more efficacious treatments for PMH. As dermatologists, and experts of the skin, it is our job to help patients with clinically challenging and personally frustrating conditions like PMH. Only with continued emphasis on clinical research, and investigation into further treatment modalities can we hope to find more information about this challenging dyschromia.

 
  References Top

1.
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;15:286-9.  Back to cited text no. 1
    
2.
Borelli D. Cutis "trunci variata." A new genetic dermatosis. Med Cutan Ibero Lat Am 1987;15:317-9.  Back to cited text no. 2
    
3.
Lesueur A, Garcia-Granel V, Hélénon R, Cales-Quist D. Progressive macular confluent hypomelanosis in mixed ethnic melanodermic subjects: An epidemiologic study of 511 patients. Ann Dermatol Venereol 1994;121:880-3.  Back to cited text no. 3
    
4.
Menke HE, Relyveld GN, Njoo D, Westerhof W. Progressive macular hypomelanosis. In: Nordlund JJ, Boissy RE, Hearing VJ, King RA, Oetting WS, Ortonne JP, editors. The Pigmentary System: Physiology and Pathophysiology. 2 nd ed. London: Blackwell Publishing Ltd.; 2006. p. 748-51.  Back to cited text no. 4
    
5.
Ortonne JP, Bahadoran P, Fitzpatrick TB, Mosher DB, Hori Y. Hypomelanoses and hypermelanoses. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, editors. Fitzpatrick's Dermatology in General Medicine. 6 th ed. New York: McGraw-Hill; 2003. p. 836-81.  Back to cited text no. 5
    
6.
Relyveld GN, Menke HE, Westerhof W. Progressive macular hypomelanosis: An overview. Am J Clin Dermatol 2007;8:13-9.  Back to cited text no. 6
    
7.
Westerhof W, Relyveld GN, Kingswijk MM, de Man P, Menke HE. Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis. Arch Dermatol 2004;140:210-4.  Back to cited text no. 7
    
8.
Cavalcanti SM, de França ER, Lins AK, Magalhães M, de Alencar ER, Magalhães V. Investigation of Propionibacterium acnes in progressive macular hypomelanosis using real-time PCR and culture. Int J Dermatol 2011;50:1347-52.  Back to cited text no. 8
    
9.
Martínez-Martínez ML, Azaña-Defez JM, Rodríguez-Vázquez M, Faura-Berruga C, Escario-Travesedo E. Progressive macular hypomelanosis. Pediatr Dermatol 2012;29:460-2.  Back to cited text no. 9
    
10.
Kim MB, Kim GW, Cho HH, Park HJ, Kim HS, Kim SH, et al. Narrowband UVB treatment of progressive macular hypomelanosis. J Am Acad Dermatol 2012;66:598-605.  Back to cited text no. 10
    
11.
Elmariah SB, Kundu RV. Progressive macular hypomelanosis. J Drugs Dermatol 2011;10:502-6.  Back to cited text no. 11
    
12.
Santos JB, Almeida OL, Silva LM, Barreto ER. Efficacy of topical combination of benzoyl peroxide 5% and clindamycin 1% for the treatment of progressive macular hypomelanosis: A randomized, doubleblind, placebo-controlled trial. An Bras Dermatol 2011;86:50-4.  Back to cited text no. 12
    
13.
Kumarasinghe SP, Tan SH, Thng S, Thamboo TP, Liang S, Lee YS. Progressive macular hypomelanosis in Singapore: A clinico-pathological study. Int J Dermatol 2006;45:737-42.  Back to cited text no. 13
    
14.
Relyveld GN, Dingemans KP, Menke HE, Bos JD, Westerhof W. Ultrastructural findings in progressive macular hypomelanosis indicate decreased melanin production. J Eur Acad Dermatol Venereol 2008;22:568-74.  Back to cited text no. 14
    
15.
Relyveld GN, Westerhof W, Woudenberg J, Kingswijk M, Langenberg M, Vandenbroucke-Grauls CM, et al. Progressive macular hypomelanosis is associated with a putative Propionibacterium species. J Invest Dermatol 2010;130:1182-4.  Back to cited text no. 15
    
16.
Tierney EP, Hamzavi I. Progressive macular hypomelanosis arising in a young African American woman in association with pregnancy and a toxic nodular goiter. J Drugs Dermatol 2010;9:393-7.  Back to cited text no. 16
    
17.
Relyveld GN, Kingswijk MM, Reitsma JB, Menke HE, Bos JD, Westerhof W. Benzoyl peroxide/clindamycin/UVA is more effective than fluticasone/UVA in progressive macular hypomelanosis: A randomized study. J Am Acad Dermatol 2006;55:836-43.  Back to cited text no. 17
    
18.
Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol 2003;49:S200-10.  Back to cited text no. 18
    
19.
Menke H, Relyveld G, Westerhof W. Comment on the letter by Chung et al. about progressive macular hypomelanosis. J Eur Acad Dermatol Venereol 2008;22:1029-30.  Back to cited text no. 19
    
20.
Fluhr JW, Gloor M. The antimicrobial effect of narrow-band UVB (313 nm) and UVA1 (345-440 nm) radiation in vitro. Photodermatol Photoimmunol Photomed 1997;13:197-201.  Back to cited text no. 20
    
21.
Kim YJ, Lee DY, Lee JY, Yoon TY. Progressive macular hypomelanosis showing excellent response to oral isotretinoin. J Dermatol 2012;39:937-8.  Back to cited text no. 21
    


    Figures

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    Tables

  [Table 1]


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