|Year : 2018 | Volume
| Issue : 2 | Page : 83-90
Idiopathic guttate hypomelanosis: An overview
Indrashis Podder1, Rashmi Sarkar2
1 Department of Dermatology, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India
2 Department of Dermatology, Maulana Azad Medical College, New Delhi, India
|Date of Web Publication||14-Dec-2018|
Dr. Indrashis Podder
Department of Dermatology, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Idiopathic guttate hypomelanosis is a commonly acquired, benign leukoderma characterized by multiple, discrete round or oval, porcelain-white macules on sun-exposed areas, especially the extensor aspect of forearms and shins, sparing the face, neck, and trunk. It usually affects the geriatric population (>50 years); chronic exposure to ultraviolet rays and senile degeneration being the important pathogenic factors. The diagnosis remains essentially clinical, whereas newer confirmatory investigations are emerging. Despite the benign course of progression, many patients seek medical attention owing to cosmetic concerns. Several treatment modalities have been tried over time including topical, physical, and surgical measures, although there is lack of a standard treatment regime. In this article, we have reviewed the different aspects of this condition including treatment, along with the recent updates to create awareness about this dermatological entity.
Keywords: Benign, geriatric, idiopathic guttate hypomelanosis, senile degeneration
|How to cite this article:|
Podder I, Sarkar R. Idiopathic guttate hypomelanosis: An overview. Pigment Int 2018;5:83-90
| Introduction|| |
Idiopathic guttate hypomelanosis (IGH) is a relatively common leukodermic dermatosis, usually affecting the elderly population. Melanopenic hypomelanosis is considered to be the basic pathomechanism. This disorder is clinically characterized by multiple, discreet round to oval, sharply defined hypopigmented to depigmented porcelain-white macules, usually ranging from 0.2 to 2 cm in diameter., The sun-exposed areas are involved most frequently, especially the extensor forearms and pretibial areas, with relative sparing of the trunk and face.,
Despite the benign nature of this condition, patients often seek medical treatment to allay their cosmetic concerns only to be reassured regarding its natural course. The treatment of this condition still remains unsatisfactory; however, newer treatment modalities are being described with each passing day. This article is aimed to provide a comprehensive review of this condition encompassing its etiopathogenesis, diagnosis, and the various treatment modalities along with relevant review of literature.
| Literature search methods|| |
We undertook a comprehensive English literature search across multiple databases such as PubMed, SCOPUS, EMBASE, MEDLINE, and Cochrane using keywords (alone and in combination) and MeSH items such as “idiopathic guttate hypomelanosis,” “acquired leukoderma,” “leukopathy,” “treatment,” and “senile depigmented spots” to obtain several relevant articles, priority being given to prospective randomized controlled trials. We scanned all the relevant articles and summarized them to obtain the latest information about this condition to prepare the current article.
| Discussion|| |
The different aspects of this condition have been discussed here along with relevant review of literature.
This condition was first described by Costa in 1951 as “symmetric progressive leukopathy of the extremities.” Subsequently, the present nomenclature was coined by Cummings and Cottel who described the condition on a larger group of patients.
This condition primarily affects the older population, increasing incidence being reported with advancing ages. The probability of acquiring IGH increases with age, ranging from 47% (31–40 years) to 97% (81–90 years).
However, this condition has also been reported in the 2nd decade, with the earliest report at 3 years.
A female preponderance has been reported, although this might be attributed to their greater cosmetic concern and prompt dermatologic consultation.
Although IGH occurs in all races, dark-skinned individuals are affected more commonly. Caucasians with brown eyes and hair are also predisposed to develop this condition.
Although the exact etiopathogenesis of IGH is yet to be elucidated, several factors have been proposed as the possible triggers as discussed below:
Increased prevalence of IGH in the elderly population may be attributed to several degenerative changes which occur as a part of the normal aging process. Several studies have demonstrated a gradual reduction in the number of melanocytes with advancing age, about 10% to 20% per decade, whereas some studies have suggested age-related somatic mutation of the melanocytes. Apart from the reduced density, defective melanocytes (both structural and functional) are also responsible for this condition, characterized by dilatation of the endoplasmic reticulum, swelling of the mitochondria, less or absent dendrites, and limited number of melanosomes., Some authors have also highlighted the role of defective keratinocytes which fail to phagocytose the melanosomes, as an additional etiologic factor. The role of senility is further corroborated by histologic evidence of skin aging in the surrounding skin such as epidermal atrophy, rete ridge flattening, and reduced epidermal keratosis.
Chronic ultraviolet exposure
The causal role of chronic exposure to ultraviolet (UV) rays has been proposed as IGH lesions occur more frequently on the sun-exposed areas. Several studies have demonstrated increased occurrence on IGH on skin, which might have been exposed to phototherapy (narrowband-UVB or psoralen and UVA monotherapy). The role of photo exposure has also been confirmed by histopathologic and ultrastructural studies, which have demonstrated solar elastosis in almost 70% of the IGH lesions, a histologic marker of chronic UV exposure. In addition, perivascular monocytic infiltration has also been reported in the lesions, which hints toward the inflammatory nature of IGH. Paradoxically, very few patients develop IGH lesions on the face and neck, although these areas are constantly exposed to the sun, probably due to different texture and thickness of the facial and neck skin, and these lesions have also been reported from sites which are scarcely exposed to sun. Thus, there is credible evidence to incriminate the role of UV radiation in IGH pathogenesis, although a definite causal role is yet to be established.
Genetic predisposition might be an etiologic factor, as evidenced by the development of IGH on sun-protected areas and in younger patients. A study on renal transplant patients demonstrated significant association between IGH and human leukocyte antigen-DQ3; however, no correlation was obtained with human leukocyte antigen-DR8. In addition, some investigators have reported increased frequency of IGH in patients with positive family history.
IGH lesions occur most frequently on the anterior tibial surfaces or on the lower central region of the back. Both these areas have minimum subcutaneous tissue and are vulnerable to local trauma (persons using body scrubs). As a result, the higher prevalence of IGH in these areas supports the etiologic role of local trauma.
Autoimmune factors have been proposed as a possible etiologic factor after Wilson et al. demonstrated the presence of antibodies against gastric parietal cells in almost one-third of IGH patients. However, this view has been contested as antithyroglobulin, antinuclear, and other common autoantibodies have been found to be normal in these patients. The recent consensus attributes positive antibodies to gastric parietal cells as an age-related change. However, further studies are needed to establish this evidence.
Local inhibition of melanogenesis
Some authors have suggested local inhibition of melanogenesis as a causal factor, rather than generalized pigmentary defect. This view has been endorsed by Falabella et al., who noted depigmentation of normal skin grafts over the IGH lesions, without spreading to the surrounding areas.
IGH presents as discreet, sharply demarcated, round-to-oval, porcelain-white, smooth (only color change, no textural abnormality) asymptomatic macules, usually ranging from 0.5 to 6 mm in diameter, which may occasionally reach up to 2.5 cm [Figure 1]. Usually these lesions do not increase in size or coalesce; however, Shin et al. have reported gradual enlargement of the lesions in 16% of their patients.
The number of lesions may range from one to more than 100 in a single patient. Significantly, younger patients with IGH have been found to harbor fewer (<5) and smaller lesions (<2 mm) as opposed to numerous (>30–50) and larger lesions (3–5 mm) in older individuals (>50 years).
IGH lesions usually have a predilection for the sun-exposed areas of our body, especially the extensor surfaces of arms and shins, rarely involving the trunk, face, and neck. In case of facial lesions, the marginal (mandibular) zone is more favored rather than the central part. Shin et al. have demonstrated lesions in both sun-protected and exposed areas in almost three-fourth of their patients. The hairs within the lesions are usually spared., Often there are associated changes of photodamage in the surrounding skin such as lentigenes and xerosis.
Recently, Kumarasinghe have described three morphological variants of IGH:
- Solitary or multiple hypopigmented macules on a background of sun-damaged skin in sun-exposed areas.
- Solitary ivory white, stellate, well-circumscribed, sclerotic macules related to sun exposure, which can also be present on covered/sun-protected areas.
- Small well-circumscribed hypopigmented macules with hyperkeratotic flat crust, often having a scalloped border.
However, detailed studies are needed to confirm whether these varieties share the same pathogenesis, or are different entities.
IGH is primarily a clinical diagnosis made on the basis of history and physical examination. Physical examination should be performed under both visible light and UV light of about 365-nm wavelength (Wood’s lamp) preferably, as these lesions may not be conspicuous under visible light in light-skinned individuals. Under Wood’s lamp, these lesions show enhanced depigmentation, confirming reduced pigmentation.
Recently, other investigations are being performed to rule out the common differential diagnoses (discussed below), most notably dermoscopy and histopathology. However, these investigations are not needed routinely.
Dermoscopy or epiluminescence microscopy is a noninvasive technique to improve the diagnostic precision in doubtful cases. A recent study by Ankad and Beergouder has described four dermoscopic patterns pertaining to IGH, namely, amoeboid, feathery, petaloid, and nebuloid patterns in descending order of frequency [Figure 2]. A combination of all these patterns was noted in almost 13.3% of the patients. A clinical correlation has also been deciphered; feathery striations in older lesions and nebuloid pattern with indistinct borders in relatively newer lesions.
|Figure 2: Dermoscopy of an IGH lesion showing amoeboid and feathery margins (Heine Mini 3000, Heine Optotechnik GMBH&Co. KG, Herrsching, Germany, 10×)|
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Histopathological examination is rarely performed to confirm the diagnosis in cases of diagnostic dilemma. A study by Kim et al. has proposed hyperkeratosis of the stratum corneum, flattened rete ridges, epidermal atrophy, and acanthosis to be suggestive of IGH. However, epidermal atrophy was more often detected in non sun-exposed areas than sun-exposed areas, which was statistically significant.
The pigmentary dilution is corroborated by reduced number and irregular distribution of melanocytes in the IGH lesions. The melanocytes in IGH have been found to be large (retained pigment due to abnormal uptake by keratinocytes) with small and retracted dendritic processes. Joshi have described a characteristic histologic finding in IGH lesions—“skipped areas of retained melanin in the basal layer alternating with large areas of melanin loss.” These findings have been confirmed by 3,4-dihydroxyl-L-phenylalanine (DOPA) staining,,,, Fontana-Masson staining, and immunohistochemical studies (reduced level of melanocyte markers such as NKI/beteb and MART-1). Other additional histologic findings which may be observed in some cases include a thicker grenz zone due to deposition of glycosaminoglycans and abundance of thick, curled, branched elastic fibers (elastosis) in the dermis.
Ultrastructural findings/electron microscopy
Electron microscopy of the lesions may be performed to decipher the ultrastructural changes only for academic/research purposes. Some of the ultramicroscopic changes include melanocyte degeneration, decreased numbers of melanosomes, attenuation or absence of melanocyte dendrites, dilatation of the endoplasmic reticulum, and swelling of the mitochondria.,
Recently, Kakepis et al. have demonstrated abnormal phagocytic activity of the keratinocytes, resulting in reduced uptake of melanocytes, despite the latter having normal structure and density. So they have proposed dysfunctional keratinocytes as possible etiology rather than abnormal melanocytes. However, further studies are needed to corroborate this view.
IGH lesions must be distinguished from other common hypopigmented/depigmented mimicking lesions, namely, vitiligo, pityriasis versicolor, progressive macular hypomelanosis, lichen sclerosus et atrophicus, guttate morphea and postinflammatory hypopigmentation by physical examination, and other diagnostic procedures [Table 1].
|Table 1: Differential diagnoses of IGH and their important diagnostic clues|
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Despite being a benign condition, it assumes great importance in the darker skin because of cosmetic concerns and the resulting psychological trauma. So, these patients often seek dermatological treatment to allay their anxiety.
Counseling regarding the benign nature of this disease is of paramount importance, which usually warrants no therapeutic intervention. However, several treatment modalities have been tried over time for rapid resolution of these lesions.
Till date, no standard treatment exists for IGH; however, several medical and surgical/physical modalities have been documented. We have reviewed the various treatment options for this condition, which have been tabulated in [Table 2].
Topical calcineurin inhibitors
Topical calcineurin inhibitors have been recently found to induce repigmentation in IGH lesions. Asawanonda et al. have depicted the beneficial effect of 1% pimecrolimus cream, whereas Rerknimitr et al. have found 0.1% topical tacrolimus to be effective after 2 and 6 months, respectively, both being applied twice daily. In both the studies, subjective and objective (measurement by colorimeter for the luminosity scale) assessments have shown statistically significant improvement vis-à-vis placebo.
Three mechanisms have been proposed as its possible mode of action-stimulation of tyrosinase activity resulting in increased synthesis of melanin, increased proliferation and migration of melanocytes to the depigmented site, and its immunosuppressive action suppressing various chronic inflammatory pathways resulting from senile degeneration.
Take home message: Although topical calcineurin inhibitors have been found to be safe and effective for the treatment of IGH, prolonged duration of therapy and high cost are the limiting factors.
Pagnoni et al. have demonstrated the efficacy of topical tretinoin in the treatment of this condition, applied once at night daily for 4 months. Initially 0.025% cream was applied for 1 week, followed by 0.05% for 1 week and 0.1% for the rest of period. Clinical improvement was noted from the second month, whereas the lesions disappeared completely at the end of 4 months. The improvement was also corroborated histologically by development of rete ridges and enhanced melanin density throughout the whole epidermis. Findings were statistically significant when compared to placebo (split-body trial). However, this study was conducted during autumn and winter, when all patients wore long-sleeved clothing.
Take home message: Topical tretinoin appears to be a safe, effective, and relative cheaper mode of therapy for IGH. Notably, sun protection is mandatory prerequisite. However, further studies are needed to substantiate this claim.
Intralesional corticosteroids were first tried by Falabella et al. almost 3 decades back, for the treatment of this condition along with lesional grafting of normal skin. Pigmentary response was noted in all grafted cases, with or without intralesional corticosteroids. The local immunosuppressive effect of corticosteroids may result in its therapeutic efficacy. A short follow-up period of 6 months was a limiting factor. However, the authors failed to find any evidence of increased melanization in the lesions.
Take home message: Intralesional corticosteroids have only been found to be effective when supplemented by skin grafting. Isolated intralesional corticosteroids have not yet been studied. So, this modality is not recommended yet, but may be used carefully, with adequate monitoring for adverse effects such as skin atrophy.
Spot peeling with 88% phenol (once a month, for 3 months) has been tried successfully by Ravikiran et al., who demonstrated repigmentation in almost 64% of lesions at the end of study. Persistent crust formation (>15 days), postinflammatory hyperpigmentation, ulceration, secondary infection, and scarring were the most common reported adverse effects, respectively.
Although exact mechanism of action is not known, two modalities have been proposed by the authors—inactivation of an inhibitory enzyme or chemokine or destruction of the epidermal keratinocytes, thus subsequently normalizing the process of melanocyte uptake once new keratinocytes are formed.
Take home message: Topical spot-peeling with 88% phenol is a safe, effective, and inexpensive treatment modality for this condition; however, this substance must be used cautiously to avoid associated cardiac toxicity.
Surgical and other physical measures
Cryotherapy has been proposed by several authors as an effective treatment modality for IGH., Repigmentation has been observed in >90% of the treated lesions after 6 to 8 weeks. Initially 10 s of cryo-freezing time was proposed, which resulted in blistering of the lesions. Subsequently, Kumarasinghe has demonstrated similar efficacy with 3 to 5 s of freeze time, without any blister. Ultrastructural studies have demonstrated increased density of melanin and DOPA-positive melanocytes after the procedure, although fewer than in normal skin.
Although the exact mechanism is debated, inactivation of melanogenesis inhibitory chemokines, destruction of defective epidermis to normalize the uptake of melanocytes by keratinocytes, and/or postinflammatory hyperpigmentation are considered to the possible modes of action.
Take home message: Cryotherapy is a low-cost, minimally invasive procedure for effective treatment of IGH. However, expert guidance is mandated to avoid deeper cryo-injury leading to scarring. Currently, a freeze time of 3 to 5 s is deemed sufficient, and vesiculation is not the end point to achieve repigmentation.
Localized, superficial dermabrasion was reported as a successful treatment modality by Hexsel et al., who achieved satisfactory repigmentation in almost 80% of study patients. Crusting developed initially, which fell off by 10 days. Best results were obtained for lesions <5 mm in diameter and those located on exposed hairy areas, the hair follicles acting as source of new melanocytes. However, the initial enthusiasm centering this procedure waned down due to development of postprocedure erythema, which persisted for almost 3 to 6 months.
Take home message: Superficial dermabrasion may be tried to resistant IGH lesions under expert supervision; however, postprocedure persistent erythema is a limiting factor.
Fractional CO2 laser
Fractional carbon dioxide laser (CO2FL) is one of the latest additions in the treatment armamentarium of IGH., The treatment settings consisted of 100-mJ pulse energy, a spot density of 150 spots/cm2 in static mode, and then two passes were delivered with a 300-spot-density tip. In the first study, almost 42.7% patients reported considerable clinical improvement, whereas in the other study, almost 90% patients reported >50% clinical improvement. Koh et al. have recently demonstrated the superiority of CO2FL over topical retinoid cream. Minor adverse effects such as pain during procedure and burning sensation resolved within next day. However, persistent erythema and postinflammatory hyperpigmentation have been reported in few patients, which is more common in the darker skin. No serious adverse effects such as infection, scarring, or aggravation have been reported in either study. Significantly, no recurrence has been noted even after 1 year following procedure.
This modality probably acts by thermal destruction of the dysfunctional melanocytes and recruitment/proliferation of normal melanocytes from the surrounding pilosebaceous units by secreting several cytokines and growth factors.
Take home message: This is a safe and effective modality for treatment of IGH with faster healing times than dermabrasion. However, high cost, restricted availability, persistent erythema, and postinflammatory hyperpigmentation are some of its limitations.
Nonablative fractional photothermolysis
Rerknimitr et al. studied the effect of nonablative fractional 1550-nm ytterbium/erbium laser on IGH to counteract the problems of erythema and postinflammatory hyperpigmentation induced by CO2FL, especially in the darker skin. The parameter setting energy ranged from 25 to 30 mJ/cm2; total density being 600 MTZ/cm2, each patient receiving four consecutive sessions at 4-week intervals. Almost 60% of the patients achieved >50% improvement. Side effects included mild erythema and edema which resolved by the next day. Significantly, no postinflammatory hyperpigmentation was observed.
The mechanism of nonablative fractional photothermolysis was proposed to be similar to that of ablative fractional laser, without ablation thus minimizing the chance of adverse effects.
Take home message: Nonablative fractional laser appears to be a good alternative treatment, especially in darker skinned individuals to avoid postinflammatory hyperpigmentation. However, high cost and limited availability are its deterrents.
Falabella et al. studied the effect of autologous skin grafting over IGH lesions, both with and without intralesional corticosteroids. Only one out of 15 lesions showed repigmentation, irrespective of administration of intralesional corticosteroids. A short follow-up period was also a limitation of this study.
Take home message: This modality is not recommended as a treatment of IGH, as more effective and safer options are available for the same.
As we can see, a plethora of treatment options have been tried for IGH over the years, with varying rates of success. However, the search for a definite treatment showing consistent results is still underway. Several innovative treatments have also been proposed for this condition lately, which seem to hold some promise. Here we have listed some of the recent therapeutic advances for this condition:
- 5-Fluorouracil (FU) tattooing—This novel form of therapy has been proposed by Wambier et al. and Arbache et al. who have used disposable sterile needles attached to a professional tattoo machine to inject 5-FU solution (50 mg/ml), until pinpoint bleeding was obtained (end point). Results were noticeable within the first month, and persistent results have been obtained after a variable and transient period of postinflammatory hyperpigmentation.
Possible mechanism of action involves regulatory effects on dermal fibroblasts or creation of a long-lasting favorable microenvironment for the melanocyte migration and pigment spread.
- Excimer laser—Gordon et al. have found excimer laser to be a satisfactory treatment option for IGH in a pilot study. In their study, most of the treated lesions achieved significant repigmentation at the end of 12 weeks.
- Placental extracts—Gupta et al. evaluated placental extracts as an adjuvant therapy to phenol for this condition. They found marginally better repigmentation with placental extracts with 88% phenol; however, the result was not statistically significant. In contrast, scarring and postinflammatory pigmentation were less in patients receiving placental extract. So, supplementing placental extract with phenol makes the treatment more acceptable to patients.
| Conclusion|| |
IGH is a commonly acquired, age-related benign leukoderma usually affecting the sun-exposed areas in the elderly population. However, many patients, usually of the darker skin types, consult a dermatologist because of their cosmetic concern. The diagnosis of this condition is primarily clinical, but dermoscopy and histopathology may be performed to rule out other differentials. Several medical, surgical, and physical modalities have been tried for this condition, with varying rates of success; but final consensus regarding treatment is still lacking. The lack of a dermatologic procedure with consistent results has resulted in many dermatologists counseling against any form of treatment. To conclude, the authors recommend topical retinoids, 88% phenol, and cryotherapy as safe and effective therapeutic options to achieve quicker repigmentation.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]