Patient Presentation
A 25-year-old man presented with a 2-year history of developing a slowly progressing symmetrical eruption comprised of multiple hyperpigmented slate gray-colored irregular patches predominantly involving the neck, upper torso and the proximal extremities. The lesions started as asymptomatic erythematous macules.
Physical examination revealed multiple, large, ash-gray hyperpigmented macules and confluent patches of different sizes and shapes, distributed predominantly over the front and sides of the neck, chest, abdomen, upper back and the proximal extremities. The palms, soles, nails, oral mucosa and the genitals were uninvolved.
There was no history of excessive sun exposure or long hours of working outdoors. There was no personal or family history of atopic diatheses. There was no history of antecedent illness or any drug intake prior to the eruption.
The rest of the physical examination and routine blood and urinalyses were unremarkable. Histopathological examination of a biopsy specimen taken from one of the lesions on the back revealed some vacuolar damage of the basal layer of the epidermis. There was a band-like mononuclear infiltrate in the superficial dermis. Melanin-laden macrophages were also found in the dermis.
What is Your Diagnosis?
Diagnosis: Ashy dermatosis
Ashy dermatosis was first described by Oswaldo Ramirez at the first Central American Congress of Dermatology in El Salvador in 1957.1 Ramirez termed the condition “dermatitis cenicienta,” meaning the ash-colored ones. The original cohort of patients almost exclusively came from Central and South America. In 1961, Convit et al described five patients with similar findings in Venezuela. In view of their beliefs that this disorder belonged to the erythema perstans group, they proposed the term “erythema dyschromicum perstans,” as originally suggested by Dr. Sulzberger.2
The first case of ashy dermatosis in the United States was reported by Stevenson and Miura in 1966.3 Subsequently, cases throughout the world were reported, and a possible association with lichen planus (LP) proposed.4,5 Other terms used in the subsequent literature include “ashy dermatosis,” “erythema chronicum figuratum melanodermicum,” and “lichen planus pigmentosus.”
Epidemiology
Ashy dermatosis occurs worldwide in all races, but appears to be more common in Latin America and Asia, favoring individuals with skin types III and IV. A slight female predominance is described.6,7 The age of onset is usually between the first to third decades of life. However, there are several reports of ashy dermatosis beginning in early childhood.8,9 To date, less than 400 cases have been reported in the English literature.
What is the Cause?
The cause of ashy dermatosis remains unknown, with no known genetic predisposition reported. Some authors have argued that it may be a variant of LP. This was based on the clinical observation that ashy dermatosis may accompany, precede or follow lesions of LP, and from the similarities shared on histology and immunofluoresence.10 However, most patients to date have never shown any lesion changes suggestive of LP.1,9,11
Immunopathologic studies have also revealed patterns in ashy dermatosis similar to lichen planus. These include Ia antigen expression on epidermal keratinocytes, pronounced OKT4 and OKT6 staining of epidermal dendritic cells, a dermal infiltration of both helper-inducer (OKT4) and suppressor-cytotoxic (OKT8) phenotypes, and positive IgG staining on colloid bodies.12,13
Several other associations have been made, such as treatment with dithiazide iodide for whipworm infestation,3 ingestion of ammonium nitrate,14 orally administered X-ray contrast media,15 cobalt allergy,16 vitiligo,17 and exposure to the fungicide chlorothalonil.18
Based on these reports, one might hypothesize that ashy dermatosis represents an inflammatory reaction to a chemical, ingested agent, or a contactant, followed by a persistent slate-colored hyperpigmentation. A viral etiology is also proposed based on anecdotal associations with chronic hepatitis C and the human immunodeficiency virus.19-22
Clinical features
Most patients present with progressive ashy-gray, gray-brown or gray-blue macules and patches.2 An erythematous peripheral margin measuring 1 mm to 2 mm in width is described. However, this border is often not present, and eventually disappears after several months. Initial lesions are asymptomatic or occasionally mildly pruritic. They are of variable size, usually measuring between
0.5 cm to 2.5 cm, but can be larger.
Lesions vary in shape from oval to round to polycyclic, often following skin cleavage lines and assuming a pattern similar to that of pityriasis rosea. Lesions may be surrounded by a pale halo accentuating the ashen color, particularly in dark-skinned individuals. Common sites of involvement include the face, neck, trunk and proximal arms, usually in a symmetrical distribution. The palms, soles, scalp, nails and mucous membranes are typically spared. A case with unilateral and asymmetric involvement affecting the left trunk and leg has also been reported.23
Pathology
The histology depends on the phase of the lesion and is not pathognomonic. Histopathology of early active borders may demonstrate lichenoid dermatitis with vacuolization of the basal layer, and at times, colloid bodies. Mild-to-moderate, perivascular lymphohistiocytic infiltrate with melanophages may occasionally be seen in the upper dermis. Exocytosis of the infiltrate into the epidermis has also been described.
In older lesions, melanin incontinence may be evident with an atrophic epidermis and discrete follicular hyperkeratosis.9 With disease progression, the inflammatory infiltrate tends to diminish with gradual loss of the rete ridges. Direct immunofluoresence microscopy studies of the active borders have demonstrated IgM, IgG, fibrinogen, and C4 staining.5,24
Other Conditions to Consider
Conditions to consider in the differential diagnosis are summarized in Table 1. Lichen planus pigmentosum (LPP) was described by Bhutani et al in 12 patients with ashy dermatosis and coincidental lichen planus.25 Vega et al reported in 1992 that LPP and ashy dermatosis are distinct entities and presented clinical differences between the two.26 LPP is distinguished by being pruritic, having brownish-black macules or patches with no active border, and generally located on the face and flexor folds. LPP may also involve the mucosal surfaces. Of note, the two disorders may be histologically indistinguishable.
Idiopathic eruptive macular pigmentation (IEMP) was first delineated by Degos et al in 1978.27 It is described as a brownish non-confluent, asymptomatic eruption of macules involving the trunk, neck and proximal extremities, with an absence of preceding inflammation and a normal mast cell count.
On histology, basal cell layer hyperpigmentation of the epidermis and prominent melanophages without visible basal layer damage or lichenoid inflammatory infiltrates are seen.
Ashy dermatosis is presumably differentiated by a history of preceding erythema and the spontaneous regression of the IEMP lesions.28 However, some authors have commented that it is conceivable that IEMP and ashy dermatosis actually represent the same condition, and clinical distinction may be impossible.9
Among the more easily differentiated possibilities, post-inflammatory hyperpigmentation differs in history, clinical course and visible features of the primary lesions. Cutaneous mastocytosis usually has a positive Darier’s sign. Pinta is confirmed by a positive dark-field examination, anti-treponemal serology, and responds to penicillin therapy. Macular amyloid is easily distinguished on histology. A fixed drug eruption may resemble ashy dermatosis, but generally has a more circular shape with a browner color.
Management
On initial consultation it is important to obtain a thorough medical history, perform an oral and genital examination, and when indicated, a punch biopsy to rule out other causes of hyperpigmentation, such as lichen planus.
A review of medications may be indicative of a fixed drug eruption. To date, no laboratory data or radiographic studies have been found helpful in diagnosis; in general, therapeutic attempts for ashy dermatosis have not been successful. Topical and systemic steroids, keratolytics, hydroquinone, dapsone, clofazimine, antibiotics, retinoids, griseofulvin, ascorbic acid, chloroquine, estrogens, chemical peels and laser therapy have been tried with variable efficacy.29
Spontaneous clearing may occur, but the lesions usually persist for years. As a general precaution, sun avoidance is advocated.
Our patient’s treatment consisted of topical clobetasol propionate 0.05% and oral clofazimine 100 mg per day. There was marked improvement in the skin coloration after 1 month of therapy. Clofazimine was well tolerated by the patient, and he was advised to continue the treatment for another 2 months.
Treatment case studies
Based on the observation that immune mechanisms are involved in the pathogenesis, Piquero-Martin et al treated eight patients with clofazimine. This anti-inflammatory agent has previously been used in the treatment of diseases such as leprosy, mycobacterial infections, and discoid lupus erythematosus. In this report, the authors noted marked improvement in skin coloration and a diminution in the CD4/CD8 count in venous peripheral blood.30 Although the mechanism of action is unclear, clofazimine produces a uniform skin coloration masking the dyschromias, and exerts immunomodulatory and anti-inflammatory effects.
Baranda et al subsequently performed a prospective study of six patients treated with clofazimine 100 mg for 3 months. Two patients discontinued, one due to adverse effects that included a reddish-orange skin discoloration and pruritus. Of the four who finished, two achieved complete clearing, and the other two were markedly improved. The medication seemed to have a greater efficacy on the early inflammatory phase of ashy dermatosis. An orange discoloration of the skin was observed in all patients toward the end of therapy, but it disappeared several weeks later. The authors commented on the disappearance of intercellular adhesion molecule 1 and HLA-DR as well as mononuclear cell infiltrates at the end of therapy.31
Aside from skin discoloration, the drug may produce ichthyosis, nausea, diarrhea, splenic infarcts, and the most notable, but rare, crystal deposition in the gut with a potentially fatal enteropathy. Overall, it is interesting to note the lack of co-occurrence of ashy dermatosis with other immune-based pathologies such as vitiligo.32
Individual case reports describe good response to dapsone, possibly by regulation of the pathogenic immune response.22,32 However, further studies are necessary.
A single report describes a patient with chronic hepatitis C who improved with a combination of interferon-alpha and ribavirin. Whether this response was related to the antiviral effects or the immunomodulatory properties of this combination is not known. 22
Berger et al described a 53-year-old woman who developed ashy dermatosis 1 year after the onset of lichen planus. She cleared on griseofulvin therapy but relapsed after discontinuation. Re-treatment with griseofulvin again resulted in clearing.10
In one report, a short course of oral prednisone reduced erythema at the boundaries, followed by partial fading of the discoloration.29
Lastly, it should be noted that some authors abstained from active treatment as none have been shown to be consistently effective, and consequently limited their interventions with their patients to verbal reassurances of both patients and their families.9
A Need for More Research
Ashy dermatosis is an infrequently reported skin lesion. To date, reports have been primarily among Hispanic and Asian patients. Considering the population numbers of these two groups, the rarity of reports may represent misdiagnosis, lower awareness or poor healthcare availability. Yet, with these two large and increasing populations in the United States, it is important to enhance the awareness and understanding of this disease.
At the moment, ashy dermatosis appears to only be limited to cosmetic discomforts. However, with further studies into the etiology and treatment of this lesion, physicians will be better able to understand and solve the intricacies at hand.
Furthermore, discovering the best treatment will benefit affected patients both locally and worldwide. To date, with such a rare occurrence of ashey dermatosis, no gold standard of therapy exists.
Also, no associated co-morbidities have been noted. Despite this fact, we encourage physicians to continue their reports and studies on this poorly understood disease.
Patient Presentation
A 25-year-old man presented with a 2-year history of developing a slowly progressing symmetrical eruption comprised of multiple hyperpigmented slate gray-colored irregular patches predominantly involving the neck, upper torso and the proximal extremities. The lesions started as asymptomatic erythematous macules.
Physical examination revealed multiple, large, ash-gray hyperpigmented macules and confluent patches of different sizes and shapes, distributed predominantly over the front and sides of the neck, chest, abdomen, upper back and the proximal extremities. The palms, soles, nails, oral mucosa and the genitals were uninvolved.
There was no history of excessive sun exposure or long hours of working outdoors. There was no personal or family history of atopic diatheses. There was no history of antecedent illness or any drug intake prior to the eruption.
The rest of the physical examination and routine blood and urinalyses were unremarkable. Histopathological examination of a biopsy specimen taken from one of the lesions on the back revealed some vacuolar damage of the basal layer of the epidermis. There was a band-like mononuclear infiltrate in the superficial dermis. Melanin-laden macrophages were also found in the dermis.
What is Your Diagnosis?
Diagnosis: Ashy dermatosis
Ashy dermatosis was first described by Oswaldo Ramirez at the first Central American Congress of Dermatology in El Salvador in 1957.1 Ramirez termed the condition “dermatitis cenicienta,” meaning the ash-colored ones. The original cohort of patients almost exclusively came from Central and South America. In 1961, Convit et al described five patients with similar findings in Venezuela. In view of their beliefs that this disorder belonged to the erythema perstans group, they proposed the term “erythema dyschromicum perstans,” as originally suggested by Dr. Sulzberger.2
The first case of ashy dermatosis in the United States was reported by Stevenson and Miura in 1966.3 Subsequently, cases throughout the world were reported, and a possible association with lichen planus (LP) proposed.4,5 Other terms used in the subsequent literature include “ashy dermatosis,” “erythema chronicum figuratum melanodermicum,” and “lichen planus pigmentosus.”
Epidemiology
Ashy dermatosis occurs worldwide in all races, but appears to be more common in Latin America and Asia, favoring individuals with skin types III and IV. A slight female predominance is described.6,7 The age of onset is usually between the first to third decades of life. However, there are several reports of ashy dermatosis beginning in early childhood.8,9 To date, less than 400 cases have been reported in the English literature.
What is the Cause?
The cause of ashy dermatosis remains unknown, with no known genetic predisposition reported. Some authors have argued that it may be a variant of LP. This was based on the clinical observation that ashy dermatosis may accompany, precede or follow lesions of LP, and from the similarities shared on histology and immunofluoresence.10 However, most patients to date have never shown any lesion changes suggestive of LP.1,9,11
Immunopathologic studies have also revealed patterns in ashy dermatosis similar to lichen planus. These include Ia antigen expression on epidermal keratinocytes, pronounced OKT4 and OKT6 staining of epidermal dendritic cells, a dermal infiltration of both helper-inducer (OKT4) and suppressor-cytotoxic (OKT8) phenotypes, and positive IgG staining on colloid bodies.12,13
Several other associations have been made, such as treatment with dithiazide iodide for whipworm infestation,3 ingestion of ammonium nitrate,14 orally administered X-ray contrast media,15 cobalt allergy,16 vitiligo,17 and exposure to the fungicide chlorothalonil.18
Based on these reports, one might hypothesize that ashy dermatosis represents an inflammatory reaction to a chemical, ingested agent, or a contactant, followed by a persistent slate-colored hyperpigmentation. A viral etiology is also proposed based on anecdotal associations with chronic hepatitis C and the human immunodeficiency virus.19-22
Clinical features
Most patients present with progressive ashy-gray, gray-brown or gray-blue macules and patches.2 An erythematous peripheral margin measuring 1 mm to 2 mm in width is described. However, this border is often not present, and eventually disappears after several months. Initial lesions are asymptomatic or occasionally mildly pruritic. They are of variable size, usually measuring between
0.5 cm to 2.5 cm, but can be larger.
Lesions vary in shape from oval to round to polycyclic, often following skin cleavage lines and assuming a pattern similar to that of pityriasis rosea. Lesions may be surrounded by a pale halo accentuating the ashen color, particularly in dark-skinned individuals. Common sites of involvement include the face, neck, trunk and proximal arms, usually in a symmetrical distribution. The palms, soles, scalp, nails and mucous membranes are typically spared. A case with unilateral and asymmetric involvement affecting the left trunk and leg has also been reported.23
Pathology
The histology depends on the phase of the lesion and is not pathognomonic. Histopathology of early active borders may demonstrate lichenoid dermatitis with vacuolization of the basal layer, and at times, colloid bodies. Mild-to-moderate, perivascular lymphohistiocytic infiltrate with melanophages may occasionally be seen in the upper dermis. Exocytosis of the infiltrate into the epidermis has also been described.
In older lesions, melanin incontinence may be evident with an atrophic epidermis and discrete follicular hyperkeratosis.9 With disease progression, the inflammatory infiltrate tends to diminish with gradual loss of the rete ridges. Direct immunofluoresence microscopy studies of the active borders have demonstrated IgM, IgG, fibrinogen, and C4 staining.5,24
Other Conditions to Consider
Conditions to consider in the differential diagnosis are summarized in Table 1. Lichen planus pigmentosum (LPP) was described by Bhutani et al in 12 patients with ashy dermatosis and coincidental lichen planus.25 Vega et al reported in 1992 that LPP and ashy dermatosis are distinct entities and presented clinical differences between the two.26 LPP is distinguished by being pruritic, having brownish-black macules or patches with no active border, and generally located on the face and flexor folds. LPP may also involve the mucosal surfaces. Of note, the two disorders may be histologically indistinguishable.
Idiopathic eruptive macular pigmentation (IEMP) was first delineated by Degos et al in 1978.27 It is described as a brownish non-confluent, asymptomatic eruption of macules involving the trunk, neck and proximal extremities, with an absence of preceding inflammation and a normal mast cell count.
On histology, basal cell layer hyperpigmentation of the epidermis and prominent melanophages without visible basal layer damage or lichenoid inflammatory infiltrates are seen.
Ashy dermatosis is presumably differentiated by a history of preceding erythema and the spontaneous regression of the IEMP lesions.28 However, some authors have commented that it is conceivable that IEMP and ashy dermatosis actually represent the same condition, and clinical distinction may be impossible.9
Among the more easily differentiated possibilities, post-inflammatory hyperpigmentation differs in history, clinical course and visible features of the primary lesions. Cutaneous mastocytosis usually has a positive Darier’s sign. Pinta is confirmed by a positive dark-field examination, anti-treponemal serology, and responds to penicillin therapy. Macular amyloid is easily distinguished on histology. A fixed drug eruption may resemble ashy dermatosis, but generally has a more circular shape with a browner color.
Management
On initial consultation it is important to obtain a thorough medical history, perform an oral and genital examination, and when indicated, a punch biopsy to rule out other causes of hyperpigmentation, such as lichen planus.
A review of medications may be indicative of a fixed drug eruption. To date, no laboratory data or radiographic studies have been found helpful in diagnosis; in general, therapeutic attempts for ashy dermatosis have not been successful. Topical and systemic steroids, keratolytics, hydroquinone, dapsone, clofazimine, antibiotics, retinoids, griseofulvin, ascorbic acid, chloroquine, estrogens, chemical peels and laser therapy have been tried with variable efficacy.29
Spontaneous clearing may occur, but the lesions usually persist for years. As a general precaution, sun avoidance is advocated.
Our patient’s treatment consisted of topical clobetasol propionate 0.05% and oral clofazimine 100 mg per day. There was marked improvement in the skin coloration after 1 month of therapy. Clofazimine was well tolerated by the patient, and he was advised to continue the treatment for another 2 months.
Treatment case studies
Based on the observation that immune mechanisms are involved in the pathogenesis, Piquero-Martin et al treated eight patients with clofazimine. This anti-inflammatory agent has previously been used in the treatment of diseases such as leprosy, mycobacterial infections, and discoid lupus erythematosus. In this report, the authors noted marked improvement in skin coloration and a diminution in the CD4/CD8 count in venous peripheral blood.30 Although the mechanism of action is unclear, clofazimine produces a uniform skin coloration masking the dyschromias, and exerts immunomodulatory and anti-inflammatory effects.
Baranda et al subsequently performed a prospective study of six patients treated with clofazimine 100 mg for 3 months. Two patients discontinued, one due to adverse effects that included a reddish-orange skin discoloration and pruritus. Of the four who finished, two achieved complete clearing, and the other two were markedly improved. The medication seemed to have a greater efficacy on the early inflammatory phase of ashy dermatosis. An orange discoloration of the skin was observed in all patients toward the end of therapy, but it disappeared several weeks later. The authors commented on the disappearance of intercellular adhesion molecule 1 and HLA-DR as well as mononuclear cell infiltrates at the end of therapy.31
Aside from skin discoloration, the drug may produce ichthyosis, nausea, diarrhea, splenic infarcts, and the most notable, but rare, crystal deposition in the gut with a potentially fatal enteropathy. Overall, it is interesting to note the lack of co-occurrence of ashy dermatosis with other immune-based pathologies such as vitiligo.32
Individual case reports describe good response to dapsone, possibly by regulation of the pathogenic immune response.22,32 However, further studies are necessary.
A single report describes a patient with chronic hepatitis C who improved with a combination of interferon-alpha and ribavirin. Whether this response was related to the antiviral effects or the immunomodulatory properties of this combination is not known. 22
Berger et al described a 53-year-old woman who developed ashy dermatosis 1 year after the onset of lichen planus. She cleared on griseofulvin therapy but relapsed after discontinuation. Re-treatment with griseofulvin again resulted in clearing.10
In one report, a short course of oral prednisone reduced erythema at the boundaries, followed by partial fading of the discoloration.29
Lastly, it should be noted that some authors abstained from active treatment as none have been shown to be consistently effective, and consequently limited their interventions with their patients to verbal reassurances of both patients and their families.9
A Need for More Research
Ashy dermatosis is an infrequently reported skin lesion. To date, reports have been primarily among Hispanic and Asian patients. Considering the population numbers of these two groups, the rarity of reports may represent misdiagnosis, lower awareness or poor healthcare availability. Yet, with these two large and increasing populations in the United States, it is important to enhance the awareness and understanding of this disease.
At the moment, ashy dermatosis appears to only be limited to cosmetic discomforts. However, with further studies into the etiology and treatment of this lesion, physicians will be better able to understand and solve the intricacies at hand.
Furthermore, discovering the best treatment will benefit affected patients both locally and worldwide. To date, with such a rare occurrence of ashey dermatosis, no gold standard of therapy exists.
Also, no associated co-morbidities have been noted. Despite this fact, we encourage physicians to continue their reports and studies on this poorly understood disease.
Patient Presentation
A 25-year-old man presented with a 2-year history of developing a slowly progressing symmetrical eruption comprised of multiple hyperpigmented slate gray-colored irregular patches predominantly involving the neck, upper torso and the proximal extremities. The lesions started as asymptomatic erythematous macules.
Physical examination revealed multiple, large, ash-gray hyperpigmented macules and confluent patches of different sizes and shapes, distributed predominantly over the front and sides of the neck, chest, abdomen, upper back and the proximal extremities. The palms, soles, nails, oral mucosa and the genitals were uninvolved.
There was no history of excessive sun exposure or long hours of working outdoors. There was no personal or family history of atopic diatheses. There was no history of antecedent illness or any drug intake prior to the eruption.
The rest of the physical examination and routine blood and urinalyses were unremarkable. Histopathological examination of a biopsy specimen taken from one of the lesions on the back revealed some vacuolar damage of the basal layer of the epidermis. There was a band-like mononuclear infiltrate in the superficial dermis. Melanin-laden macrophages were also found in the dermis.
What is Your Diagnosis?
Diagnosis: Ashy dermatosis
Ashy dermatosis was first described by Oswaldo Ramirez at the first Central American Congress of Dermatology in El Salvador in 1957.1 Ramirez termed the condition “dermatitis cenicienta,” meaning the ash-colored ones. The original cohort of patients almost exclusively came from Central and South America. In 1961, Convit et al described five patients with similar findings in Venezuela. In view of their beliefs that this disorder belonged to the erythema perstans group, they proposed the term “erythema dyschromicum perstans,” as originally suggested by Dr. Sulzberger.2
The first case of ashy dermatosis in the United States was reported by Stevenson and Miura in 1966.3 Subsequently, cases throughout the world were reported, and a possible association with lichen planus (LP) proposed.4,5 Other terms used in the subsequent literature include “ashy dermatosis,” “erythema chronicum figuratum melanodermicum,” and “lichen planus pigmentosus.”
Epidemiology
Ashy dermatosis occurs worldwide in all races, but appears to be more common in Latin America and Asia, favoring individuals with skin types III and IV. A slight female predominance is described.6,7 The age of onset is usually between the first to third decades of life. However, there are several reports of ashy dermatosis beginning in early childhood.8,9 To date, less than 400 cases have been reported in the English literature.
What is the Cause?
The cause of ashy dermatosis remains unknown, with no known genetic predisposition reported. Some authors have argued that it may be a variant of LP. This was based on the clinical observation that ashy dermatosis may accompany, precede or follow lesions of LP, and from the similarities shared on histology and immunofluoresence.10 However, most patients to date have never shown any lesion changes suggestive of LP.1,9,11
Immunopathologic studies have also revealed patterns in ashy dermatosis similar to lichen planus. These include Ia antigen expression on epidermal keratinocytes, pronounced OKT4 and OKT6 staining of epidermal dendritic cells, a dermal infiltration of both helper-inducer (OKT4) and suppressor-cytotoxic (OKT8) phenotypes, and positive IgG staining on colloid bodies.12,13
Several other associations have been made, such as treatment with dithiazide iodide for whipworm infestation,3 ingestion of ammonium nitrate,14 orally administered X-ray contrast media,15 cobalt allergy,16 vitiligo,17 and exposure to the fungicide chlorothalonil.18
Based on these reports, one might hypothesize that ashy dermatosis represents an inflammatory reaction to a chemical, ingested agent, or a contactant, followed by a persistent slate-colored hyperpigmentation. A viral etiology is also proposed based on anecdotal associations with chronic hepatitis C and the human immunodeficiency virus.19-22
Clinical features
Most patients present with progressive ashy-gray, gray-brown or gray-blue macules and patches.2 An erythematous peripheral margin measuring 1 mm to 2 mm in width is described. However, this border is often not present, and eventually disappears after several months. Initial lesions are asymptomatic or occasionally mildly pruritic. They are of variable size, usually measuring between
0.5 cm to 2.5 cm, but can be larger.
Lesions vary in shape from oval to round to polycyclic, often following skin cleavage lines and assuming a pattern similar to that of pityriasis rosea. Lesions may be surrounded by a pale halo accentuating the ashen color, particularly in dark-skinned individuals. Common sites of involvement include the face, neck, trunk and proximal arms, usually in a symmetrical distribution. The palms, soles, scalp, nails and mucous membranes are typically spared. A case with unilateral and asymmetric involvement affecting the left trunk and leg has also been reported.23
Pathology
The histology depends on the phase of the lesion and is not pathognomonic. Histopathology of early active borders may demonstrate lichenoid dermatitis with vacuolization of the basal layer, and at times, colloid bodies. Mild-to-moderate, perivascular lymphohistiocytic infiltrate with melanophages may occasionally be seen in the upper dermis. Exocytosis of the infiltrate into the epidermis has also been described.
In older lesions, melanin incontinence may be evident with an atrophic epidermis and discrete follicular hyperkeratosis.9 With disease progression, the inflammatory infiltrate tends to diminish with gradual loss of the rete ridges. Direct immunofluoresence microscopy studies of the active borders have demonstrated IgM, IgG, fibrinogen, and C4 staining.5,24
Other Conditions to Consider
Conditions to consider in the differential diagnosis are summarized in Table 1. Lichen planus pigmentosum (LPP) was described by Bhutani et al in 12 patients with ashy dermatosis and coincidental lichen planus.25 Vega et al reported in 1992 that LPP and ashy dermatosis are distinct entities and presented clinical differences between the two.26 LPP is distinguished by being pruritic, having brownish-black macules or patches with no active border, and generally located on the face and flexor folds. LPP may also involve the mucosal surfaces. Of note, the two disorders may be histologically indistinguishable.
Idiopathic eruptive macular pigmentation (IEMP) was first delineated by Degos et al in 1978.27 It is described as a brownish non-confluent, asymptomatic eruption of macules involving the trunk, neck and proximal extremities, with an absence of preceding inflammation and a normal mast cell count.
On histology, basal cell layer hyperpigmentation of the epidermis and prominent melanophages without visible basal layer damage or lichenoid inflammatory infiltrates are seen.
Ashy dermatosis is presumably differentiated by a history of preceding erythema and the spontaneous regression of the IEMP lesions.28 However, some authors have commented that it is conceivable that IEMP and ashy dermatosis actually represent the same condition, and clinical distinction may be impossible.9
Among the more easily differentiated possibilities, post-inflammatory hyperpigmentation differs in history, clinical course and visible features of the primary lesions. Cutaneous mastocytosis usually has a positive Darier’s sign. Pinta is confirmed by a positive dark-field examination, anti-treponemal serology, and responds to penicillin therapy. Macular amyloid is easily distinguished on histology. A fixed drug eruption may resemble ashy dermatosis, but generally has a more circular shape with a browner color.
Management
On initial consultation it is important to obtain a thorough medical history, perform an oral and genital examination, and when indicated, a punch biopsy to rule out other causes of hyperpigmentation, such as lichen planus.
A review of medications may be indicative of a fixed drug eruption. To date, no laboratory data or radiographic studies have been found helpful in diagnosis; in general, therapeutic attempts for ashy dermatosis have not been successful. Topical and systemic steroids, keratolytics, hydroquinone, dapsone, clofazimine, antibiotics, retinoids, griseofulvin, ascorbic acid, chloroquine, estrogens, chemical peels and laser therapy have been tried with variable efficacy.29
Spontaneous clearing may occur, but the lesions usually persist for years. As a general precaution, sun avoidance is advocated.
Our patient’s treatment consisted of topical clobetasol propionate 0.05% and oral clofazimine 100 mg per day. There was marked improvement in the skin coloration after 1 month of therapy. Clofazimine was well tolerated by the patient, and he was advised to continue the treatment for another 2 months.
Treatment case studies
Based on the observation that immune mechanisms are involved in the pathogenesis, Piquero-Martin et al treated eight patients with clofazimine. This anti-inflammatory agent has previously been used in the treatment of diseases such as leprosy, mycobacterial infections, and discoid lupus erythematosus. In this report, the authors noted marked improvement in skin coloration and a diminution in the CD4/CD8 count in venous peripheral blood.30 Although the mechanism of action is unclear, clofazimine produces a uniform skin coloration masking the dyschromias, and exerts immunomodulatory and anti-inflammatory effects.
Baranda et al subsequently performed a prospective study of six patients treated with clofazimine 100 mg for 3 months. Two patients discontinued, one due to adverse effects that included a reddish-orange skin discoloration and pruritus. Of the four who finished, two achieved complete clearing, and the other two were markedly improved. The medication seemed to have a greater efficacy on the early inflammatory phase of ashy dermatosis. An orange discoloration of the skin was observed in all patients toward the end of therapy, but it disappeared several weeks later. The authors commented on the disappearance of intercellular adhesion molecule 1 and HLA-DR as well as mononuclear cell infiltrates at the end of therapy.31
Aside from skin discoloration, the drug may produce ichthyosis, nausea, diarrhea, splenic infarcts, and the most notable, but rare, crystal deposition in the gut with a potentially fatal enteropathy. Overall, it is interesting to note the lack of co-occurrence of ashy dermatosis with other immune-based pathologies such as vitiligo.32
Individual case reports describe good response to dapsone, possibly by regulation of the pathogenic immune response.22,32 However, further studies are necessary.
A single report describes a patient with chronic hepatitis C who improved with a combination of interferon-alpha and ribavirin. Whether this response was related to the antiviral effects or the immunomodulatory properties of this combination is not known. 22
Berger et al described a 53-year-old woman who developed ashy dermatosis 1 year after the onset of lichen planus. She cleared on griseofulvin therapy but relapsed after discontinuation. Re-treatment with griseofulvin again resulted in clearing.10
In one report, a short course of oral prednisone reduced erythema at the boundaries, followed by partial fading of the discoloration.29
Lastly, it should be noted that some authors abstained from active treatment as none have been shown to be consistently effective, and consequently limited their interventions with their patients to verbal reassurances of both patients and their families.9
A Need for More Research
Ashy dermatosis is an infrequently reported skin lesion. To date, reports have been primarily among Hispanic and Asian patients. Considering the population numbers of these two groups, the rarity of reports may represent misdiagnosis, lower awareness or poor healthcare availability. Yet, with these two large and increasing populations in the United States, it is important to enhance the awareness and understanding of this disease.
At the moment, ashy dermatosis appears to only be limited to cosmetic discomforts. However, with further studies into the etiology and treatment of this lesion, physicians will be better able to understand and solve the intricacies at hand.
Furthermore, discovering the best treatment will benefit affected patients both locally and worldwide. To date, with such a rare occurrence of ashey dermatosis, no gold standard of therapy exists.
Also, no associated co-morbidities have been noted. Despite this fact, we encourage physicians to continue their reports and studies on this poorly understood disease.
