CAMEO
LEUKODERMIC MACULES IN KERATOSIS EOLLICULARIS (DARIER'S DISEASE) W.K. JACYK, M.D., AND A.J. VISSER, M.D.
Four black African patients, two men and two women, were seen. Patient 1 was a Dinka from the southern Sudan studied in 1981. Patients 2, 3, and 4 were seen in the period 1986 to 1990 in South Africa. On examination all four patients had typical lesions of keratosis follicularis consisting of firm, greasy, crusted keratotic papules in the seborrheic areas of the trunk and face, with coalescing lesions on the scalp. The manifestations of keratosis follicularis differed in extent and severity. Acrokeratosis verruciformis-iike lesions on the shins and nail changes were observed in ail four patients. Involvement of the volar aspects of the hands and feet was variable, ranging from none, through delicate pits, to severely disabling plantar keratoderma. The oral mucosa was involved in only one patient. All four patients had widespread guttate markedly hypopigmented macules most prominent on the abdomen and chest (Figs. 1 and 2). In two patients the anterior aspects of the thighs and legs were also involved. The macules ranged from 1 to 4 mm in diameter and were distributed mainly in a perifoUicular pattern. In three patients the macules were discrete, while in one they coalesced to form thin reticulate strands. The leukodermic macules occurred in areas where classic papules of keratosis follicularis were absent or very sparse. They had not been preceded by papular keratotic lesions and appeared to evolve separately from them. During a 5year follow-up of patient 2, we observed the development of keratotic papules in some areas previously affected only by leukodermic macules. They erupted selectively between the macular elements. In all four patients the lesions started to appear in the first decade of life with both papules and hypopigmented macules erupting approximately at the same time and running a parallel course. A positive family history of keratosis follicularis was present in one patient.
Figure 1. Leukodermic macules on the chest, and keratotic papules on the neck and in the preauricular area (case 2).
Electron microscopy: Two biopsies from leukodermic macules were examined (patients 2 and 3). No abnormalities were found in a biopsy from patient 3, whereas in patient 2 some melanosomes appeared to be morphologically abnormal in that they tended to be spherical and irregularly shaped rather than ellipsoid. Both melanosomes within melanocytes and within keratinocytes were affected. Within melanocytes, melanosomes in stages II and III predominated. Apart from the melanosome abnormalities no specific pathology was seen.
Histopathology: Light microscopy of papular lesions from all four patients showed a picture of keratosis follicularis. Eight biopsies were taken of the leukodermic lesions, three each of patients 2 and 3 and one each in patients 1 and 4. The hematoxylin-eosin stain In two biopsies of patient 3 revealed suprabasal clefting (Fig. 3). The third biopsy of this patient, as well as those of all remaining patients, revealed only a decrease of melanin in the basal layer of the epidermis.
From the Department of Dermatology, Kalafong Hospital, and Ga-Rankuwa Hospital, Pretoria, Republic of South Africa.
Treatment: Patient 1 was treated with aqueous vitamin A, 200,000 IU daily for 8 weeks, and patient 2 was given two 6month courses of etretinate (1-1.5 mg/kg/day). In both cases improvement of the follicular keratotic lesions was noticed without any influence on the leukodermic macules.
Address for correspondence: W.K. Jacyk, M.D., Department of Dermatology, Kalafong Hospital, Private Bag X396, 0001 Pretoria, Republic of South Africa. 715
International Journal of Dermatology Vol, 31, No, 10, October 1992
Figure 2. (case 4).
Figure 3. Histology of a leukodermic macule on the chest. Suprabasal cleft (case 3). (hematoxylin and eosin stain, original magnification x 80)
Glose-up of leukodcrniic macuies on the chest
DISCUSSION
;
•
^
The presence of leukodermic macuies appears to be an extremely rare occurrence in keratosis follicularis and only six cases have been reported to date (Table 1).'"^ All patients with keratosis follicularis and leukodermic macuies had heavily pigmented skin; eight were of negroid African descent, one Latin-American, and one Indian or Pakistani. In all patients the leukodermic macuies were most profuse on the trunk with less prominent involvement of the proximal parts of the lower extremities. In our four cases, leukodermic macuies were present mainly on the anterior surface of the chest, abdomen, thighs, and legs. Previous reports did not emphasize a predominant ventral distribution, but
Small leukodermic macuies on the trunk and limbs are a very rare feature of keratosis follicularis (Darier's disease). Since the first description by Goddal and Richmond in 1965,' five further cases have been reported.^^ Berth-Jones and Hutchinson"* have recently drawn attention to the selective perifollicular distribution ofthe leukodermic lesions. Keratosis follicularis is a well-defined disorder of keratinization with characteristic clinical and histopathologic features. All forms, including the most common classic type and the less frequent linear, hypertrophic, cornifying, and bullous variants, are transmitted as an autosomal dominant trait.
Table 1. Reports of Leukodermic Macuies in Keratosis Follicularis Pattern and Distribution of Leukodermic Macuies
Reference No.
Sex
Race
1
F
Black
2
M
Black
F
Black
M
Black
M
LatinTrunk and extremities American Asian Perifollicular. Trunk and proximal parts of extremities
' 3
M
Present Gases
Tiny, in bran-like pattern. Trunk and upper extremities Intermingled with classic keratotic papules. Trunk Peri- and interfollicular. Trunk and extremities Trunk and extremities
F
Black
Abdomen
M
Black
F
Black
Intermingled with keratotic papules. Abdomen, chest, lower extremities Abdomen, chest, thighs, legs
M
Black
Goalescing in some areas into thin strands. Ghest, lower extremities
Histology Not done Epidermal thinning, decrease number of melanocytes Marked decrease in melanin in the basal layer Marked decrease in melanin in the basal layer Not done
Keratosis Follicularis Glassic Glassic, mucosai lesions, nail changes Glassic, palmoplanter pits, nail changes Glassic, nail changes Glassic
Suprabasal clefting with Glassic, palmopiantar acantholytic cells, corps ronds, pits, nail changes decreased number of melanocytes Decrease in melanin Glassic, oral lesions, nail changes Decrease in melanin Glassic, plantar pits, nail changes Suprabasal clefting Decrease in melanin Decrease in melanin
716
Glassic, nail changes, family history of keratosis follicularis Glassic, plantar pits, severe plantar keratoderma, nail changes
Keratosis Follicularis Jacyk and Visser
in no patient were the leukodermic macuies described as occurring on the back, buttocks, or posterior aspect of the extremities. In the patient of Berth-Jones and Hutchinson,'' leukodermic macuies were the only lesions of keratosis follicularis on the trunk, and it was striking that they occurred in a perifollicular pattern. In our patients, the leukodermic macuies were also predominantly perifollicular. The histology of a leukodermic lesion in the patient of Berth-Jones and Hutchinson'' showed the typical features of keratosis follicularis. In one of our patients, two leukodermic macuies were biopsied, and both demonstrated suprabasal clefting. In all the remaining reported cases, as well as in our three patients, the only observed histopathologic abnormality was a decrease in pigmentation. The pigmentary status of lesions of keratosis follicularis has been the subject of several studies, and reduced pigmentation is a recognized histopathologic feature of an early papular lesion.^'* In our four patients, as well as in other cases,^-'' the leukodermic macuies did not occur at the sites of previous papular lesions, which makes Cattano's explanation of postinflammatory changes unlikely.' The demonstration of suprabasal clefting in the leukodermic macule of one of our patients supports Berth-Jones and Hutchinson's suggestion that these lesions may represent a subclinical form of the disease.'' The electron microscopic findings require confirmation to draw conclusions that there is an abnormal formation of melanosomes.
Administration of etretinate in one of our patients led to temporary improvement of the keratotic lesions without influencing the leukodermic macuies. One of Cornelison's patients' and one of our patients have been treated with oral vitamin A with similar effect. Acknowledgment: The Electron Microscopy Unit of the South African Institute for Medical Research, Johannesburg, assisted.
REFERENCES
1. 2. 3. 4.
5.
6.
Goddal JW, Richmond QM, A case of Darier's disease. BrJ Glin Pract 1965; 19:475-476. Gattano AN. An unusual case of keratosis follicularis. Arch Dermatol 1968; 98:168-174, Gornelison RL, Smith EB, Knox JM, Guttate leukoderma in Darier's disease. Arch Dermatol 1970; 102: 447^50. Berth-Jones J, Hutchinson PE. Darier's disease with perifollicular depigmentation. Br J Dermatol 1989; 120:827-830. Perin LS. Histologie d'une tache pigmentaire au course de la maladie de Darier. Bull Soc Franc Dermatol Syphiligr 1934; 41:28-32. Douwes FR. Zur Histologie und Histochemie des Morbus Darier. Arch Klin Exp Dermatol 1968; 233: 309-322.
Scorbutic Ulcers The putrid or scorbutic ulcer proved to be one of the most troublesome, inveterate, and dangerous diseases which afflicted the British seamen employed in the Leeward Islands during the late war. The ravages which I have seen made by it, as well in naval hospitals as on board the fleet; the many opportunities I had of comparing different methods of treatment, and of observing the most eligible; and the duty I owe to humanity in general, and the naval service of my country in particular, all induce me to lay before the public a few remarks on this complaint. I prefer the name of putrid ulcer to any other, because the marks of putrescency always were evident to the senses, although those of scurvy were not. It, in general, did not attack the ships crews until they had been at least a year in the West Indies; and it often seemed to rage epidemically on board certain ships, whilst others remained, in a great measure, free from it: thus His Majesty's ships Ajax, Montagu, Ruffel, and Triumph, in the beginning of 1781, landed a great number of men on Pigeon Island, St. Lucia, with ulcers of the most malignant nature, whilst several ships in the fleet, which had been employed the same length of time, in the same climate, and on the same service, remained, in a great measure, free from such complaints. It often affected those who began to recover from fever or dysentery, and those who had other symptoms of scurvy; but it often occurred to those who had been healthy during their continuance in the West Indies, and most generally after having received a wound or contusion, however slight, particularly of the lower extremities. From Gillespie L. Observations on the putrid ulcer. Lond Med] 1785; 6:373-402. 717
LEUKODERMIC MACULES IN KERATOSIS EOLLICULARIS (DARIER'S DISEASE) W.K. JACYK, M.D., AND A.J. VISSER, M.D.
Four black African patients, two men and two women, were seen. Patient 1 was a Dinka from the southern Sudan studied in 1981. Patients 2, 3, and 4 were seen in the period 1986 to 1990 in South Africa. On examination all four patients had typical lesions of keratosis follicularis consisting of firm, greasy, crusted keratotic papules in the seborrheic areas of the trunk and face, with coalescing lesions on the scalp. The manifestations of keratosis follicularis differed in extent and severity. Acrokeratosis verruciformis-iike lesions on the shins and nail changes were observed in ail four patients. Involvement of the volar aspects of the hands and feet was variable, ranging from none, through delicate pits, to severely disabling plantar keratoderma. The oral mucosa was involved in only one patient. All four patients had widespread guttate markedly hypopigmented macules most prominent on the abdomen and chest (Figs. 1 and 2). In two patients the anterior aspects of the thighs and legs were also involved. The macules ranged from 1 to 4 mm in diameter and were distributed mainly in a perifoUicular pattern. In three patients the macules were discrete, while in one they coalesced to form thin reticulate strands. The leukodermic macules occurred in areas where classic papules of keratosis follicularis were absent or very sparse. They had not been preceded by papular keratotic lesions and appeared to evolve separately from them. During a 5year follow-up of patient 2, we observed the development of keratotic papules in some areas previously affected only by leukodermic macules. They erupted selectively between the macular elements. In all four patients the lesions started to appear in the first decade of life with both papules and hypopigmented macules erupting approximately at the same time and running a parallel course. A positive family history of keratosis follicularis was present in one patient.
Figure 1. Leukodermic macules on the chest, and keratotic papules on the neck and in the preauricular area (case 2).
Electron microscopy: Two biopsies from leukodermic macules were examined (patients 2 and 3). No abnormalities were found in a biopsy from patient 3, whereas in patient 2 some melanosomes appeared to be morphologically abnormal in that they tended to be spherical and irregularly shaped rather than ellipsoid. Both melanosomes within melanocytes and within keratinocytes were affected. Within melanocytes, melanosomes in stages II and III predominated. Apart from the melanosome abnormalities no specific pathology was seen.
Histopathology: Light microscopy of papular lesions from all four patients showed a picture of keratosis follicularis. Eight biopsies were taken of the leukodermic lesions, three each of patients 2 and 3 and one each in patients 1 and 4. The hematoxylin-eosin stain In two biopsies of patient 3 revealed suprabasal clefting (Fig. 3). The third biopsy of this patient, as well as those of all remaining patients, revealed only a decrease of melanin in the basal layer of the epidermis.
From the Department of Dermatology, Kalafong Hospital, and Ga-Rankuwa Hospital, Pretoria, Republic of South Africa.
Treatment: Patient 1 was treated with aqueous vitamin A, 200,000 IU daily for 8 weeks, and patient 2 was given two 6month courses of etretinate (1-1.5 mg/kg/day). In both cases improvement of the follicular keratotic lesions was noticed without any influence on the leukodermic macules.
Address for correspondence: W.K. Jacyk, M.D., Department of Dermatology, Kalafong Hospital, Private Bag X396, 0001 Pretoria, Republic of South Africa. 715
International Journal of Dermatology Vol, 31, No, 10, October 1992
Figure 2. (case 4).
Figure 3. Histology of a leukodermic macule on the chest. Suprabasal cleft (case 3). (hematoxylin and eosin stain, original magnification x 80)
Glose-up of leukodcrniic macuies on the chest
DISCUSSION
;
•
^
The presence of leukodermic macuies appears to be an extremely rare occurrence in keratosis follicularis and only six cases have been reported to date (Table 1).'"^ All patients with keratosis follicularis and leukodermic macuies had heavily pigmented skin; eight were of negroid African descent, one Latin-American, and one Indian or Pakistani. In all patients the leukodermic macuies were most profuse on the trunk with less prominent involvement of the proximal parts of the lower extremities. In our four cases, leukodermic macuies were present mainly on the anterior surface of the chest, abdomen, thighs, and legs. Previous reports did not emphasize a predominant ventral distribution, but
Small leukodermic macuies on the trunk and limbs are a very rare feature of keratosis follicularis (Darier's disease). Since the first description by Goddal and Richmond in 1965,' five further cases have been reported.^^ Berth-Jones and Hutchinson"* have recently drawn attention to the selective perifollicular distribution ofthe leukodermic lesions. Keratosis follicularis is a well-defined disorder of keratinization with characteristic clinical and histopathologic features. All forms, including the most common classic type and the less frequent linear, hypertrophic, cornifying, and bullous variants, are transmitted as an autosomal dominant trait.
Table 1. Reports of Leukodermic Macuies in Keratosis Follicularis Pattern and Distribution of Leukodermic Macuies
Reference No.
Sex
Race
1
F
Black
2
M
Black
F
Black
M
Black
M
LatinTrunk and extremities American Asian Perifollicular. Trunk and proximal parts of extremities
' 3
M
Present Gases
Tiny, in bran-like pattern. Trunk and upper extremities Intermingled with classic keratotic papules. Trunk Peri- and interfollicular. Trunk and extremities Trunk and extremities
F
Black
Abdomen
M
Black
F
Black
Intermingled with keratotic papules. Abdomen, chest, lower extremities Abdomen, chest, thighs, legs
M
Black
Goalescing in some areas into thin strands. Ghest, lower extremities
Histology Not done Epidermal thinning, decrease number of melanocytes Marked decrease in melanin in the basal layer Marked decrease in melanin in the basal layer Not done
Keratosis Follicularis Glassic Glassic, mucosai lesions, nail changes Glassic, palmoplanter pits, nail changes Glassic, nail changes Glassic
Suprabasal clefting with Glassic, palmopiantar acantholytic cells, corps ronds, pits, nail changes decreased number of melanocytes Decrease in melanin Glassic, oral lesions, nail changes Decrease in melanin Glassic, plantar pits, nail changes Suprabasal clefting Decrease in melanin Decrease in melanin
716
Glassic, nail changes, family history of keratosis follicularis Glassic, plantar pits, severe plantar keratoderma, nail changes
Keratosis Follicularis Jacyk and Visser
in no patient were the leukodermic macuies described as occurring on the back, buttocks, or posterior aspect of the extremities. In the patient of Berth-Jones and Hutchinson,'' leukodermic macuies were the only lesions of keratosis follicularis on the trunk, and it was striking that they occurred in a perifollicular pattern. In our patients, the leukodermic macuies were also predominantly perifollicular. The histology of a leukodermic lesion in the patient of Berth-Jones and Hutchinson'' showed the typical features of keratosis follicularis. In one of our patients, two leukodermic macuies were biopsied, and both demonstrated suprabasal clefting. In all the remaining reported cases, as well as in our three patients, the only observed histopathologic abnormality was a decrease in pigmentation. The pigmentary status of lesions of keratosis follicularis has been the subject of several studies, and reduced pigmentation is a recognized histopathologic feature of an early papular lesion.^'* In our four patients, as well as in other cases,^-'' the leukodermic macuies did not occur at the sites of previous papular lesions, which makes Cattano's explanation of postinflammatory changes unlikely.' The demonstration of suprabasal clefting in the leukodermic macule of one of our patients supports Berth-Jones and Hutchinson's suggestion that these lesions may represent a subclinical form of the disease.'' The electron microscopic findings require confirmation to draw conclusions that there is an abnormal formation of melanosomes.
Administration of etretinate in one of our patients led to temporary improvement of the keratotic lesions without influencing the leukodermic macuies. One of Cornelison's patients' and one of our patients have been treated with oral vitamin A with similar effect. Acknowledgment: The Electron Microscopy Unit of the South African Institute for Medical Research, Johannesburg, assisted.
REFERENCES
1. 2. 3. 4.
5.
6.
Goddal JW, Richmond QM, A case of Darier's disease. BrJ Glin Pract 1965; 19:475-476. Gattano AN. An unusual case of keratosis follicularis. Arch Dermatol 1968; 98:168-174, Gornelison RL, Smith EB, Knox JM, Guttate leukoderma in Darier's disease. Arch Dermatol 1970; 102: 447^50. Berth-Jones J, Hutchinson PE. Darier's disease with perifollicular depigmentation. Br J Dermatol 1989; 120:827-830. Perin LS. Histologie d'une tache pigmentaire au course de la maladie de Darier. Bull Soc Franc Dermatol Syphiligr 1934; 41:28-32. Douwes FR. Zur Histologie und Histochemie des Morbus Darier. Arch Klin Exp Dermatol 1968; 233: 309-322.
Scorbutic Ulcers The putrid or scorbutic ulcer proved to be one of the most troublesome, inveterate, and dangerous diseases which afflicted the British seamen employed in the Leeward Islands during the late war. The ravages which I have seen made by it, as well in naval hospitals as on board the fleet; the many opportunities I had of comparing different methods of treatment, and of observing the most eligible; and the duty I owe to humanity in general, and the naval service of my country in particular, all induce me to lay before the public a few remarks on this complaint. I prefer the name of putrid ulcer to any other, because the marks of putrescency always were evident to the senses, although those of scurvy were not. It, in general, did not attack the ships crews until they had been at least a year in the West Indies; and it often seemed to rage epidemically on board certain ships, whilst others remained, in a great measure, free from it: thus His Majesty's ships Ajax, Montagu, Ruffel, and Triumph, in the beginning of 1781, landed a great number of men on Pigeon Island, St. Lucia, with ulcers of the most malignant nature, whilst several ships in the fleet, which had been employed the same length of time, in the same climate, and on the same service, remained, in a great measure, free from such complaints. It often affected those who began to recover from fever or dysentery, and those who had other symptoms of scurvy; but it often occurred to those who had been healthy during their continuance in the West Indies, and most generally after having received a wound or contusion, however slight, particularly of the lower extremities. From Gillespie L. Observations on the putrid ulcer. Lond Med] 1785; 6:373-402. 717
