Dermatológica 150: 355-359 (1975)
Incontinentia Pigmenti et Achromians R a dh a M it t a l , F. H a nd a an d S ubhash C h a n d er S harma Department of Dermato-Venereology, Rajendra Hospital and Government Medical College, Patiala, Punjab
Key Words. Incontinentia pigmenti et achromians • Incontinentia pigmenti • Incon tinentia pigmenti achromians • Sex-linked inheritance • ‘Splash’ pattern • Ectodermal defect Abstract. A case is reported, apparently the first of its kind in the literature, of a female child in which there were not only pigmented lesions of incontinentia pigmenti but also hypopigmented lesions of incontinentia pigmenti achromians. The title incontinentia pigmenti et achromians is suggested for this combined disorder. The child also had asso ciated lesions in the form of nail dystrophy, delayed dentition and epilepsy.
Incontinentia pigmenti (IP) is a complex hereditary syndrome that presents in the first few weeks of life with three clinical stages, namely, vesicular, verrucous and pigmented lesions. It occurs mostly in females and usually is fatal in males. Certain other developmental defects are associated, namely, nail dystrophy, cicatricial alopecia and dental, ophthalmic, central nervous system and skeletal defects. Incontinentia pigmenti achromians (IPA) has been described hitherto as a separate though related entity which is rarely seen. The importance of the present case lies in the occurrence together of pigmented and hypopigmented lesions in the same patient which is being reported for the first time in the literature. B a r d a ch [1] is credited with being the first to report, in 1925, IP in identical twins, and he named the disease as ‘systematised nevus’. N aegeli [14] in 1927 reported three cases. An heredofamilial incidence was first
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Received: December 2, 1974; accepted: April 3, 1975.
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stressed by S ulzberg er [19] in 1938 while reporting the condition in three generations of a family. S obel [20] in 1948 stressed that the disease can occur also in males and that they too can transmit it. K itam ura el at. [6] reported in 1954 that the three clinical stages of the disease can present irregularly, each being of variable duration, and can even overlap occasionally. So far, three cases have been reported from India; by L ahiri [9] in 1955, M arquis and M ehta [11] in 1969, and R atan S in g h and D evinder K au r [18] in 1970. C u r th and W a rburton [2] in 1965 discussed the heredofamilial nature of the disease and its occurrence only in females. Regarding its mode of inheritance, P feiffer [17] in 1960 explained that it is due to an autosomal dominant sexlinked gene affecting only the females. Males seem to be unaffected as none survives pregnancy. Regarding affliction of males, L e n z [I0] in 1961 suggested that ordinarily this disease is lethal in males, resulting in abortion. However, occasionally the males show unusual resistance to this gene and present with the disease in the first few weeks after birth. Sex-linked inheritance was also supported by M arty el at. [12] in 1958 while reporting three generations of a family in which all females displayed cutaneous lesions. 1PA has been reported mostly from Japan, and the six case reports from there so far were by I to [5] in 1952, K ato el at. [7] in 1954. N o ha ra and T a saka [15] in 1961, M asum izu [13] in 1963, O kuw a and K itam ura [16] in 1966, and H amada et al. [4] in 1967. All of these cases were in females and two of them also had mental, skeletal and ocular defects. C arney and C arney [3] in 1970 reviewed 26 patients of IP to show that they had only inflammatory bullous and pigmented warty bands and that no vesicular stage was seen. Increased numbers of Merkel cells in the basal layer in cases of IP have recently been reported by K id d and W ilg ra m [8]. Our interest in reporting the present case stems from the presentation in the same individual of hyperpigmented and hypopigmented lesions which fully fit into both the syndromes, i.e. IP and 1PA, respectively; this opens up a new field in the subject not touched so far in the literature.
Case Report
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History. A female child, aged 2 years and 8 months, was admitted to the skin in patient section of the Rajcndra Hospital, Patiala, on 20th September, 1974. She presented with linear, irregular, splashed hyperpigmented lesions mainly in her axillae, popliteal fossae and groins, and on her neck and lower trunk, present since the age of 1 month; she also had had hypopigmented lesions on her trunk and upper and lower limbs since the age of 3 months. Her parents give the history that, at the age of 15 days, the child had
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Incontinentia Pigmenti et Achromians
had erythematous papules which had changed to pigmented lesions over the course of 15 days, and had subsequently become rough surfaced; they also said that when she was 3 months old, hypopigmented lesions had appeared at separate sites. Her first tooth (lower left incisor) had erupted at the age of 1 year 15 days. The child had had first epileptic fit at the age of 2 years and subsequently had two more, one at the age of 2 years 7 months and the other at 2 years 1'A months. The sensory and motor milestones were not delayed. Family history. She is the second issue of the couple and was a full-term normal vaginal delivery. The mother’s first pregnancy had produced a stillborn female child after an 8month and 10-day gestation period. General physical examination. No other congenital anomaly was detected and on examination of the cardiovascular, central nervous and skeletal systems and of the eyes, including ophthalmoscopy and dentition, no significant abnormality was detected. Dermatological findings. There are papular lesions with a slaty-brown, linear, irregularly ‘splashed’ pattern of pigmentation in both axillae, popliteal fossae and groins, and on the neck as well as the ventral and dorsal surfaces of the lower trunk (fig. I). At places, these lesions are in the form of warty bands. In addition, there are hypopigmented, linear, irregular, ‘splash'-patterned lesions over the back mainly, but also on adjoining parts of the upper and lower limbs and on the abdomen (fig. 2). They are flush with the surface. The intervening skin at both places is normal. Finger and toe nails arc dystrophic. There is neither lyniphadenopathy nor sensory loss.
►■
Fig. I. Hyperpigmcnted lesions in axillae, cubital fossae, wrists, groin, abdomen and hypopigmented lesions on abdomen. Fig. 2. Hypopigmented lesions on back and adjoining part of limbs and hyperpigmented lesions over buttocks and wrists.
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2
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M it t a l /H a n d a /S harm a
Laboratory investigations. (1) Hb, 10.0 g%. (2) TLC and DLC, normal range. (3) Urine and stools, normal. (4) ESR, 50 mm 1st h (Westcrgren). (5) X-rays of skull, humerus, femur and tibia were normal. (6a) Histopathology from hyperpigmented lesions shows hyperkeratosis, acanthosis, intraepithelial vesicles associated with spongiosis, incontinence of pigment in upper dermis and non-specific chronic infiltrate. Histopathological appearance is consistent with that of IP. (fib) Histopathology from hypopigmented lesions shows spongiosis and acanthosis with less pigment in basal layer. No incontinence of pigment was present in the dermis. Histological appearance is consistent with IPA.
Discussion Incontinence of pigment leading to IP of Bloch-Sulzberger and IPA of Ito are two well-known but related dermatoses and have been reported in different members of the same family. Both are based on a developmental ectodermal defect and have been thought to have the same pathogenesis as was suggested by H amada et al. [4] in 1967 on account of the close similarity of cutaneous, mental, dental, ocular and skeletal defects in the two condi tions. This receives further support from our case where both of these defects have occurred in the same individual. It may be pointed out here that both types of lesion have appeared independently of each other in our case and that there is no conversion of one into the other. All reported cases of IPA have been females, and our case also is a female child. Another interesting point is that, though no vesicles were seen clinically, yet in the histopathology acanthosis, intraepithelial vesicles and incontinence of pigment were seen simultaneously. This indicates that vesicular, pigmentary and warty lesions can overlap. Ackno wledgements We are indebted to the Department of Pathology, which helped us in histopathological study of the case. We are also thankful to Mr. O.P. K hosla, who prepared the photographs of the case.
1 B ardach, M.: Systematisierte Naevusbildungen bei einem eineiigen Zwillingspaar. Z. Kinderheilk. 39: 542 (1925). 2 C urth , H.O. and W arburtok, D .: The genetics of incontinentia pigmenti. Archs Derm. 92: 229 (1965). 3 C arney, R.G. and C arney, R.G., j r .: Incontinentia pigmenti. Archs Derm. ¡02: 157 (1970).
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References
Incontinentia Pigmenti et Achromians
359
4 H amada, T .; S aito, T.; S ugai, T., et a i : Incontinentia pigmenti achromians (Ito). Archs Derm. 96: 673 (1967). 5 Ito, M.: Studies on melanin: incontinentia pigmenti achromians: a singular case of nevus depigmentosus systematicus bilateralis, Tohoku J. exp. Med. 55: suppi., p. 57 (1952). 6 K itamura, K.; F ukushiro, R., and M iyabayashi, T .: Incontinentia pigmenti in Ja pan: introduction of 21 cases, Arch. Derm. Syph. 69: 667 (1954). 7 K ato, T. ; I waki, T., and G oto, T.A.: A case of incontinentia pigmenti achromians. Jap. Derm. Urol. 8: 214 (1954). 8 K idd , R.L. and W ilgram , G.I.: Incontinentia pigmenti. Archs Derm. 105: 767 (1972). 9 L ahiri, K.D.: Incontinentia pigmenti. Br. J. Derm. 67: 310 (1955). 10 L enz, W. : Zur Genesis der Incontinentia pigmenti. Annls paediat. 196: 149 (1961). 11 M arquis, L. and M ehta, T.K.: A case report o f incontinentia pigmenti. Indian J. Derm. Vener. 35: 206 (1969). 12 M arty, S.D.; Bechtel, B., and W ood, C.E.: Incontinentia pigmenti. Archs Derm. 78: 607 (1958). 13 M asumizu, T. : Incontinentia pigmenti achromians (Ito), series B. Jap. J. Derm. 73: 303 (1963). 14 N aegeli, O. : Familiärer chromatophorer Naevus. Schweiz, med. Wschr. 57:48 (1927). 15 N ohara, N. and T asaka, S.: A case report of incontinentia pigmenti achromians. Acta derm.-vener., Stockh. 56: 136 (1961). 16 O kuwa , H. and K itamura, S. : Incontinentia pigmenti achromians, series A. Jap. J. Derm. 76: 606 (1966). 17 P feiffer, R.A.: Zur Frage der Vererbung der Incontinentia Pigmenti Bloch-Siemens. Z. mensch. Vererb.-KonstitLehre 35: 469 (I960). 18 R atan Singh and D evinder K au r : Incontinentia pigmenti. Indian J. Derm. Vener., 36: 53 (1970). 19 S ulzberger, M.B.: Incontinentia pigmenti. Arch. Derm. Syph. 38: 57 (1938). 20 Sobel, N. : Incontinentia pigmenti. Arch. Derm. Syph. 58: 467 (1948).
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Dr. (Mrs.) R adha M ittal, c/ o Dr. R.L. M ittal, 5-Baradari Gardens, Patiala-147001, Punjab (India)
Incontinentia Pigmenti et Achromians R a dh a M it t a l , F. H a nd a an d S ubhash C h a n d er S harma Department of Dermato-Venereology, Rajendra Hospital and Government Medical College, Patiala, Punjab
Key Words. Incontinentia pigmenti et achromians • Incontinentia pigmenti • Incon tinentia pigmenti achromians • Sex-linked inheritance • ‘Splash’ pattern • Ectodermal defect Abstract. A case is reported, apparently the first of its kind in the literature, of a female child in which there were not only pigmented lesions of incontinentia pigmenti but also hypopigmented lesions of incontinentia pigmenti achromians. The title incontinentia pigmenti et achromians is suggested for this combined disorder. The child also had asso ciated lesions in the form of nail dystrophy, delayed dentition and epilepsy.
Incontinentia pigmenti (IP) is a complex hereditary syndrome that presents in the first few weeks of life with three clinical stages, namely, vesicular, verrucous and pigmented lesions. It occurs mostly in females and usually is fatal in males. Certain other developmental defects are associated, namely, nail dystrophy, cicatricial alopecia and dental, ophthalmic, central nervous system and skeletal defects. Incontinentia pigmenti achromians (IPA) has been described hitherto as a separate though related entity which is rarely seen. The importance of the present case lies in the occurrence together of pigmented and hypopigmented lesions in the same patient which is being reported for the first time in the literature. B a r d a ch [1] is credited with being the first to report, in 1925, IP in identical twins, and he named the disease as ‘systematised nevus’. N aegeli [14] in 1927 reported three cases. An heredofamilial incidence was first
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:22:55 AM
Received: December 2, 1974; accepted: April 3, 1975.
356
M it t a l /H a n d a /S harma
stressed by S ulzberg er [19] in 1938 while reporting the condition in three generations of a family. S obel [20] in 1948 stressed that the disease can occur also in males and that they too can transmit it. K itam ura el at. [6] reported in 1954 that the three clinical stages of the disease can present irregularly, each being of variable duration, and can even overlap occasionally. So far, three cases have been reported from India; by L ahiri [9] in 1955, M arquis and M ehta [11] in 1969, and R atan S in g h and D evinder K au r [18] in 1970. C u r th and W a rburton [2] in 1965 discussed the heredofamilial nature of the disease and its occurrence only in females. Regarding its mode of inheritance, P feiffer [17] in 1960 explained that it is due to an autosomal dominant sexlinked gene affecting only the females. Males seem to be unaffected as none survives pregnancy. Regarding affliction of males, L e n z [I0] in 1961 suggested that ordinarily this disease is lethal in males, resulting in abortion. However, occasionally the males show unusual resistance to this gene and present with the disease in the first few weeks after birth. Sex-linked inheritance was also supported by M arty el at. [12] in 1958 while reporting three generations of a family in which all females displayed cutaneous lesions. 1PA has been reported mostly from Japan, and the six case reports from there so far were by I to [5] in 1952, K ato el at. [7] in 1954. N o ha ra and T a saka [15] in 1961, M asum izu [13] in 1963, O kuw a and K itam ura [16] in 1966, and H amada et al. [4] in 1967. All of these cases were in females and two of them also had mental, skeletal and ocular defects. C arney and C arney [3] in 1970 reviewed 26 patients of IP to show that they had only inflammatory bullous and pigmented warty bands and that no vesicular stage was seen. Increased numbers of Merkel cells in the basal layer in cases of IP have recently been reported by K id d and W ilg ra m [8]. Our interest in reporting the present case stems from the presentation in the same individual of hyperpigmented and hypopigmented lesions which fully fit into both the syndromes, i.e. IP and 1PA, respectively; this opens up a new field in the subject not touched so far in the literature.
Case Report
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History. A female child, aged 2 years and 8 months, was admitted to the skin in patient section of the Rajcndra Hospital, Patiala, on 20th September, 1974. She presented with linear, irregular, splashed hyperpigmented lesions mainly in her axillae, popliteal fossae and groins, and on her neck and lower trunk, present since the age of 1 month; she also had had hypopigmented lesions on her trunk and upper and lower limbs since the age of 3 months. Her parents give the history that, at the age of 15 days, the child had
357
Incontinentia Pigmenti et Achromians
had erythematous papules which had changed to pigmented lesions over the course of 15 days, and had subsequently become rough surfaced; they also said that when she was 3 months old, hypopigmented lesions had appeared at separate sites. Her first tooth (lower left incisor) had erupted at the age of 1 year 15 days. The child had had first epileptic fit at the age of 2 years and subsequently had two more, one at the age of 2 years 7 months and the other at 2 years 1'A months. The sensory and motor milestones were not delayed. Family history. She is the second issue of the couple and was a full-term normal vaginal delivery. The mother’s first pregnancy had produced a stillborn female child after an 8month and 10-day gestation period. General physical examination. No other congenital anomaly was detected and on examination of the cardiovascular, central nervous and skeletal systems and of the eyes, including ophthalmoscopy and dentition, no significant abnormality was detected. Dermatological findings. There are papular lesions with a slaty-brown, linear, irregularly ‘splashed’ pattern of pigmentation in both axillae, popliteal fossae and groins, and on the neck as well as the ventral and dorsal surfaces of the lower trunk (fig. I). At places, these lesions are in the form of warty bands. In addition, there are hypopigmented, linear, irregular, ‘splash'-patterned lesions over the back mainly, but also on adjoining parts of the upper and lower limbs and on the abdomen (fig. 2). They are flush with the surface. The intervening skin at both places is normal. Finger and toe nails arc dystrophic. There is neither lyniphadenopathy nor sensory loss.
►■
Fig. I. Hyperpigmcnted lesions in axillae, cubital fossae, wrists, groin, abdomen and hypopigmented lesions on abdomen. Fig. 2. Hypopigmented lesions on back and adjoining part of limbs and hyperpigmented lesions over buttocks and wrists.
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2
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M it t a l /H a n d a /S harm a
Laboratory investigations. (1) Hb, 10.0 g%. (2) TLC and DLC, normal range. (3) Urine and stools, normal. (4) ESR, 50 mm 1st h (Westcrgren). (5) X-rays of skull, humerus, femur and tibia were normal. (6a) Histopathology from hyperpigmented lesions shows hyperkeratosis, acanthosis, intraepithelial vesicles associated with spongiosis, incontinence of pigment in upper dermis and non-specific chronic infiltrate. Histopathological appearance is consistent with that of IP. (fib) Histopathology from hypopigmented lesions shows spongiosis and acanthosis with less pigment in basal layer. No incontinence of pigment was present in the dermis. Histological appearance is consistent with IPA.
Discussion Incontinence of pigment leading to IP of Bloch-Sulzberger and IPA of Ito are two well-known but related dermatoses and have been reported in different members of the same family. Both are based on a developmental ectodermal defect and have been thought to have the same pathogenesis as was suggested by H amada et al. [4] in 1967 on account of the close similarity of cutaneous, mental, dental, ocular and skeletal defects in the two condi tions. This receives further support from our case where both of these defects have occurred in the same individual. It may be pointed out here that both types of lesion have appeared independently of each other in our case and that there is no conversion of one into the other. All reported cases of IPA have been females, and our case also is a female child. Another interesting point is that, though no vesicles were seen clinically, yet in the histopathology acanthosis, intraepithelial vesicles and incontinence of pigment were seen simultaneously. This indicates that vesicular, pigmentary and warty lesions can overlap. Ackno wledgements We are indebted to the Department of Pathology, which helped us in histopathological study of the case. We are also thankful to Mr. O.P. K hosla, who prepared the photographs of the case.
1 B ardach, M.: Systematisierte Naevusbildungen bei einem eineiigen Zwillingspaar. Z. Kinderheilk. 39: 542 (1925). 2 C urth , H.O. and W arburtok, D .: The genetics of incontinentia pigmenti. Archs Derm. 92: 229 (1965). 3 C arney, R.G. and C arney, R.G., j r .: Incontinentia pigmenti. Archs Derm. ¡02: 157 (1970).
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References
Incontinentia Pigmenti et Achromians
359
4 H amada, T .; S aito, T.; S ugai, T., et a i : Incontinentia pigmenti achromians (Ito). Archs Derm. 96: 673 (1967). 5 Ito, M.: Studies on melanin: incontinentia pigmenti achromians: a singular case of nevus depigmentosus systematicus bilateralis, Tohoku J. exp. Med. 55: suppi., p. 57 (1952). 6 K itamura, K.; F ukushiro, R., and M iyabayashi, T .: Incontinentia pigmenti in Ja pan: introduction of 21 cases, Arch. Derm. Syph. 69: 667 (1954). 7 K ato, T. ; I waki, T., and G oto, T.A.: A case of incontinentia pigmenti achromians. Jap. Derm. Urol. 8: 214 (1954). 8 K idd , R.L. and W ilgram , G.I.: Incontinentia pigmenti. Archs Derm. 105: 767 (1972). 9 L ahiri, K.D.: Incontinentia pigmenti. Br. J. Derm. 67: 310 (1955). 10 L enz, W. : Zur Genesis der Incontinentia pigmenti. Annls paediat. 196: 149 (1961). 11 M arquis, L. and M ehta, T.K.: A case report o f incontinentia pigmenti. Indian J. Derm. Vener. 35: 206 (1969). 12 M arty, S.D.; Bechtel, B., and W ood, C.E.: Incontinentia pigmenti. Archs Derm. 78: 607 (1958). 13 M asumizu, T. : Incontinentia pigmenti achromians (Ito), series B. Jap. J. Derm. 73: 303 (1963). 14 N aegeli, O. : Familiärer chromatophorer Naevus. Schweiz, med. Wschr. 57:48 (1927). 15 N ohara, N. and T asaka, S.: A case report of incontinentia pigmenti achromians. Acta derm.-vener., Stockh. 56: 136 (1961). 16 O kuwa , H. and K itamura, S. : Incontinentia pigmenti achromians, series A. Jap. J. Derm. 76: 606 (1966). 17 P feiffer, R.A.: Zur Frage der Vererbung der Incontinentia Pigmenti Bloch-Siemens. Z. mensch. Vererb.-KonstitLehre 35: 469 (I960). 18 R atan Singh and D evinder K au r : Incontinentia pigmenti. Indian J. Derm. Vener., 36: 53 (1970). 19 S ulzberger, M.B.: Incontinentia pigmenti. Arch. Derm. Syph. 38: 57 (1938). 20 Sobel, N. : Incontinentia pigmenti. Arch. Derm. Syph. 58: 467 (1948).
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Dr. (Mrs.) R adha M ittal, c/ o Dr. R.L. M ittal, 5-Baradari Gardens, Patiala-147001, Punjab (India)
