Time for a Churchillian approach to idiopathic guttate hypomelanosis?

By Warren R. Heymann, MD
Jan. 22, 2018

I was only 10 years old when Winston Churchill died, but even as a child I was aware of his inspirational abilities. I was reminded his gift watching Gary Oldman portray the former Prime Minister in Darkest Hour, which recounted his fierceness in never giving in to the Germans, as the Brits were determining how to return their troops from Dunkirk. Although not in the movie, I recalled his quote:

Success consists of going from failure to failure without loss of enthusiasm.

I lost my enthusiasm for treating idiopathic guttate hypomelanosis (IGH) long ago. Sir Winston would not have been proud. Perhaps it is time to reconsider some options for treating IGH.

The following is a modified abstract from the excellent review of IGH by Juntongjin et al (1):

Idiopathic guttate hypomelanosis is a common acquired leukoderma characterized by multiple, discrete round or oval, porcelain-white macules on sun-exposed areas, especially on the extensor surface of forearms and pretibial areas. It usually affects individuals aged over 40 years and the likelihood of acquiring it increases with age. The exact pathogenesis remains controversial. However, there are several factors that are believed to be involved such as aging, ultraviolet exposure, trauma, genetic factors [HLA-DQ3], autoimmunity, and local inhibition of melanogenesis. Despite the benign course of progression, many patients visit medical centers owing to cosmetic concerns and to confirm the natural course of idiopathic guttate hypomelanosis. Because there is no standard therapy for this condition, numerous medical and surgical treatments including intralesional corticosteroids, topical retinoids, topical calcineurin inhibitors, phenol peeling, cryotherapy, superficial dermabrasion, skin grafting, and ablative and non-ablative lasers have been tested with mixed results.

I have seen patients presenting with well-demarcated hypopigmented papules that may be considered as a hyperkeratotic variant of IGH. (2)

Histologically, hyperkeratosis, an atrophic epidermis, flattened rete ridges, decreased melanin content and reduced numbers of melanocytes have been reported. In a histopathologic study of 27 Korean patients with IGH, hyperkeratosis was frequently found (38%); however, the other “characteristic” findings such as epidermal atrophy (10.6%) and flattened rete ridges (14.9%) were relatively rare compared to normal skin. (3) Electron microscopy demonstrates that melanocytes and melanosomes are normal in structure. In some areas, a reduced uptake of melanosomes by the keratinocytes is observed. The authors contend that because no significant structural abnormality of melanocytes is observed, IGH is due to a functional defect in the transfer of melanosomes from melanocytes to keratinocytes.

In the dermis, fibroblasts appear structurally normal, as do most elastic and collagen fibers, although there are focal elastotic changes. (4) Other features such as collagen bundle homogenization and inflammatory cell infiltration are unremarkable. (3) Histologic features of scars are not observed. (1)

This commentary was prompted by recent literature about successful treatments for IGH.

Gordon et al performed a longitudinal, split-body controlled, single-blinded pilot study of 6 patients treated with the excimer laser for 12 weeks using a vitiligo protocol. Effectiveness was graded by the blinded observer scale through photographic comparisons at the end of the study. Lesions that received the excimer treatment had significantly higher repigmentation compared with baseline and untreated lesions. (5)

A single session of cryosurgery, administered by cotton-tip application for 5 seconds, was administered to 43 lesions with 58 assigned as control. At the fourth month, 82% of the treated lesions significantly demonstrated more than 75% improvement compared to only 2% improvement in the control population. (6)

Arbache et al utilized a microneedling technique to deliver 5-fluorouracil (5-FU) in eight patients with IGH. They found that IGH repigmentation was statistically higher for those treated with 5-FU (75.3% repigmentation) versus placebo (33.8% repigmentation). Their rationale in using 5-FU was based on their prior work noting varying degrees of papillary dermal fibrosis. (7) I reviewed that article they were referring to – there was no mention of scarring in the histologic description; the images in my copy of the article were not of the quality where I could make an accurate assessment. (8)

As noted above, in other studies, scarring does not seem to be an important histologic feature of IGH. 5-FU, in addition to other chemotherapeutic agents, has been known to cause hyperpigmentation, possibly by upregulation of melanocyte stimulating hormone. (9) Maybe it is not necessary deliver the drug by microneedling – perhaps a trial of a retinoid combined with topical 5-FU could be performed to determine if obviating procedural delivery of the drug could be of value.

Think of Winston Churchill when your patient returns with their recalcitrant disorders, seeking your help. I once asked a terribly pruritic patient why he kept scheduling appointments when I did not help him at all. He said, “if anyone will figure it out, it’s you. Keep trying something new, and I’ll keep coming back.” Patients love physicians who never, never give up.

1. Juntongijin P, et al. Idiopathic guttate hypomelanosis: A review of its etiology, pathogenesis, findings, and treatments. Am J Clin Dermatol 2016; 17: 403-11.
2. Kim SK, et al. Hypopigmented keratosis: Is it a hyperkeratotic variant of idiopathic guttate hypomelanosis? Clin Exp Dermatol 38: 526-9.
3. Kim SK, et al. Comprehensive understanding of idiopathic guttate hypomelanosis: Clinical and histopathological correlation. Int J Dermatol 2010; 49: 162-66.
4. Kakepis M, et al. Idiopathic guttate hypomelanosis: An electron microscopy study. J Eur Acad Dermatol Venereol 2015; 29: 1435-8.
5. Gordon JRS, et al. Excimer light treatment for idiopathic guttate hypomelanosis: A pilot study. Dermatol Surg 2017; 43: 553-7.
6. Laosakul K, Juntongjin P. Efficacy of tip cryosurgery in the treatment of idiopathic guttae hypomelanosis (IGH): A randomized, controlled, evaluator-blinded study. J Dermatolog Treat 2017; 28: 271-275.
7. Arbache S, et al. Activation of melanocytes in idiopathic guttate hypomelanosis after 5-fluorouracil infusion using a tattoo machine: Preliminary analysis of a randomized, split-body, single blinded, placebo controlled trial. J Am Acad Dermatol 2018; 78: 212-5.
8. Falabella R, et al. On the pathogenesis of idiopathic guttate hypomelanosis. J Am Acad Dermatol 1987; 16: 35-44.
9. Co ML, Esteban M. Lingual hyperpigmentation after 5-fluoruracil chemotherapy. BMJ Case Rep 2017; Apr 22: 2017.