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Bathing-suit ichthyosis. A peculiar phenotype of lamellar ichthyosis in South African blacks

European Journal of Dermatology. Volume 15, Number 6, 433-6, November-December 2005, Genes and skin

Summary

Author(s) : Witold K Jacyk , Department of Dermatology, University of Pretoria, Pretoria, Republic of South Africa.

Summary : Autosomal recessive congenital ichthyosis is a heterogeneous group of disorders of cornification showing a wide spectrum of clinical phenotypes.Here, thirteen cases of a so far unreported distinct type of autosomal recessive congenital ichthyosis are described. All the skin lesions were present at birth and ten were then compatible with collodion baby. Shedding of the collodion led to an ichthyotic condition with a very characteristic distribution of the lesions which involved the trunk, the most proximal parts of the upper limbs, scalp and neck but spared the central face and extremities. The term “bathing-suit” ichthyosis is suggested for this unusual phenotype of lamellar ichthyosis.

Keywords : autosomal recessive congenital ichthyosis, bathing-suit ichthyosis, lamellar ichthyosis

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ARTICLE

Auteur(s) : Witold K Jacyk

Department of Dermatology, University of Pretoria, Pretoria, Republic of South Africa

accepté le 22 Juin 2005

The term autosomal recessive congenital ichthyosis (ARCI) describes conditions sharing the basic clinical characteristic of skin scaling, usually over the entire body and often associated with erythema. Molecular studies disclosed mutations in several genes mapped to different chromosomes. Mutations in the gene TGM1 encoding the transglutaminase-1 cause the vast majority of cases of ARCI [1, 2].Transglutaminase-1 is a cross-linking enzyme essential for the formation of cornified cell envelope in the epidermis. Several different mutations of TGM-1 have been identified.More recently mutations in genes other than that of TGM1 have been also reported to cause ARCI. Mutations in lipoxygenase-3 (ALOXE-3) and 12 (R)-lipoxygenase (ALOX-12B) genes [3] as well as in the transporter ABCA 12 gene [4] were reported as the causative gene mutations in ARCI. Lipoxygenase genes encode enzymes that catalyze the oxygenation of free esterified polyunsaturated fatty acids while ABCA transporter genes bind ATP for transport of various molecules across the cell membranes. It appears so far that there are no definitive phenotypic features specific to a particular genetic defect.Autosomal recessive congenital ichthyosis shows a wide spectrum of clinical phenotypes. Patients are often born as collodion babies. In some there is erythroderma and scaling after shedding of the collodion membrane. The scales in this phenotype are fine, white or light grey. In other patients there is no redness of the skin after shedding of the collodion membrane and scales are large and dark-grey.Traditionally these two types have been named nonbullous congenital ichthyosiform erythroderma (ICIE) and lamellar ichthyosis (LI). Regardless of the type of scaling, usually the whole body is affected. Ectropion and eclabion are often present but they are usually mild. Palmoplantar keratoderma is common and of variable severity. The skin changes remain static through the patient’s life or tend to improve with age. There are no extracutaneous associated abnormalities.An unusual type of LI with the lesions restricted to the bathing-suit areas and with sparing of the limbs and face is often seen in South African black patients, much more often than other well-known types of ARCI.The only short note on this phenotype has been made in 1972 by Scott [5], then a dermatologist in Bloemfontein, South Africa.The purpose of the present report is to describe the clinical features of thirteen patients with this form of lamellar ichthyosis.

Materials and methods

All thirteen patients described in this report have been seen for the past 15 years at the Department of Dermatology, University of Pretoria. The criteria for their inclusion were the following:

i) lamellar ichthyosis with large dark-grey or brownish scales affecting the trunk and sparing the extremities and central face;
ii) a family history consistent with autosomal recessive inheritance;
iii) absence of associated features (nonsyndromic ichthyosis).

Results

The age of the patients when seen for the first time varied from 2 days to 28 years. Eight patients were then below the age of ten years. There were 2 siblings in the group and in addition, one parent gave a history of one more child, already deceased, similarly affected. The parents were all healthy. Consanguinuity in the families was denied but both parents of 10 patients belonged to the same ethnic group and came from the same rural area, often from the same village. There were 9 girls and 4 boys. These family findings are consistent with an autosomal recessive mode of inheritance. Interestingly, 7 patients belonged to Nguni ethnic groups (Zulu, Swazi, Xhosa) which do not prevail in the region where the study was conducted.

In all patients the skin lesions were present at birth and parents of 8 of them gave a description of the skin lesions at birth of their children compatible with collodion baby. Two children seen in the first week of life presented as collodion babies. ( Figure 1A-C ) taken at 2 days, 15 days and 6 months of life demonstrate a collodion baby with subsequent development of bathing-suit ichthyosis.

The distribution of the ichthyotic lesions was very characteristic- involvement of the trunk, the most proximal parts of the upper limbs, including the axillae, partial involvement of the scalp and neck with sparing of central face (figures 2 and 3). The scales were dark-brown, large and plate-like. Palms and soles were dry and diffusely mildly hyperkeratotic. The dorsal aspects of the hands and feet looked normal. The nails were not changed. One patient in whom the ichthyotic lesions were also present on the forehead had ectropion. His extrafacial ichthyosis did not differ from other patients. There were no other cutaneous or extracutaneous abnormalities. One patient, a 20-year-old woman had dermatomyositis.

Biopsies for light microscopy were taken from the lower back in 7 patients. The histopathological findings are shown in table 1( Table 1 ). There was marked hyperakeratosis, no parakeratosis, granular layer of 1 to 3 layers of cells, mild to moderate acanthosis and mild lymphocytic infiltrate in the upper dermis ( (figure 4) ). Biopsies for electron microscopy collected in three most recently seen patients did not reveal cholesterol clefts nor lipid droplets in the thickened corneal layer.

Three patients have been followed-up for a few years. Only topical descaling agents were used. The severity of their condition was stable.
Table 1 Histologic features in 7 patients with bathing-suit ichthyosis

Patient	Hyperkeratosis	Parakeratosis	Number of layer of cells in str. granul.	Acanthosis	Lymphocytic infiltrate
1	++	–	2-3	+	+
2	++	–	2-3	+	+
3	++	–	2	+/–	+
4	++	–	1-2	++	+
5	++	–	1-2	+	+
6	+	–	1	+	+
7	++	–	1	+	+

Discussion

In the light of the presently available molecular data, the traditional classification of ARCI based on clinical and ultrastructural data [6-8], which distinguish two major clinical types NCIE and LI appears to be outdated. These molecular data, however, also do not correspond consistently with phenotypic findings.

Patients with TGM 1 mutations present most often a phenotype described as classical LI [1, 2]. However, normal keratinocyte TGM 1 activity has been also reported in patients with this phenotype [9, 10]. Akiyama et al. [11] hypothesized that total loss of TGM 1 activity might lead to classic LI phenotype and partial loss to milder forms of LI or a phenotype of NCIE.

Patients with lipoxygenase genes mutations reported by Jobard et al. [3] had a phenotype similar to NCIE in young age and more like LI in adults. Moroccan and Mallian patients with mutations in transporter ABCA 12 gene reported by Lefevre et al. [4] presented a generalized ichthyosis. The scales were large and darkly pigmented.

The patients presented in this report had a very consistent phenotype as far as the distribution and appearance of the lesions are concerned. The restriction of the ichthyotic lesions to the trunk, involvement of the axillae and sparing of the limbs and central face appears unique.

The reports on the molecular findings in patients with localized ARCI are scanty. A patient demonstrating a somewhat similar phenotype to our patients, a 56-year-old Japanese woman has been described by Akiyama et al. [12] Dark-grey, thick, lamellar scales covered the neck, abdomen, center of the back and both axillae. The face and extremities appeared normal. However, she apparently had normal skin at birth and in early infancy. Two compound heterozygous mutations in TGM 1 have been identified in this patient. In another Japanese report [13], a 21-year-old man was born with mild erythroderma which was later replaced by brown, slate-like scales on the ventral surface of the trunk and in the restricted areas of the extremities. Two heterozygous missense mutations in TGM1 gene have been found in this patient, one of them identical to mutation found in a patient of Akiyama et al. [12].

Molecular studies could not been performed so far in our patients. It would be interesting whether such studies can confirm our assumption that we are dealing with a new distinct type of ichthyosis.

Ten of our patients were born as collodion babies. After shedding of the collodion, ichthyosis in bathing-suit areas developed. This evolution is reminiscent of self-healing collodion babies. Raghunath et al. [14] showed the compound heterozygous missense mutations in TGM1 gene as the cause of self-healing collodion babies.

References

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2 Russell LJ, DiGiovanna JJ, Rogers GR, Steinert PM, Hashem N, Compton JG, et al. Mutations in gene for transglutaminase 1 in autosomal lamellar ichthyosis. Nature Genet 1995; 9: 279-83.

3 Jobard F, Lefevre C, Karaduman A, Blanchet-Bardon C, Emre S, Weissenbach J, et al. Lipoxygenase-3 (ALOXE-3) and 12 (R)-Lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCLE). Linked to chromosome 17p13.1. Hum Mol Genet 2002; 11: 107-13.

4 Lefevre C, Audebert S, Jobard F, Boudjar B, Lakhdar H, Boughdene-Stambouli O, Blanchet-Bardon C, Heilig R, Foglio M, Weissenbach J, Lathrop M, Prud’homme JF, Fischer J. Mutations in the transported ABCA 12 are associated with lamellar ichthyosis type 2. Hum Mol Genet 2003; 12: 2369-78.

5 Scott F. Skin Diseases in the South African Bantu. In: Marshall J, ed. Essays on Tropical Dermatology, Vol 2. Amsterdam: Excerpta Medica, 1972: 1-17.

6 Traupe H. In: The ichthyosis, a guide to clinical diagnosis, genetic counseling and therapy. Berlin: Springer, 1989: 121-34.

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9 Huber M, Rettler I, Bernasconi K, Wyss M, Hohl D. Lamellar ichthyosis is genetically heterogenous-cases with normal keratinocyte transglutaminase. J Invest Dermatol 1995; 105: 653-4.

10 Cserhalmi-Friedman PB, Milstone LM, Christiano AM. Diagnosis of autosomal lamellar ichthyosis with mutations in TGM1 gene. Br J Dermatol 2001; 144: 726-30.

11 Akiyama M, Sawamura D, Shimizu H. The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis. Clin Exp Dermatol 2003; 28: 235-40.

12 Akiyama M, Takizawa Y, Suzuki Y, Ishiko A, Mutsuo I, Shimizu H. Compound heterozygous TGM1 mutations including a novel missense mutation L2040 in a mild form of lamellar ichthyosis. J Invest Dermatol 2001; 116: 992-5.

13 Muramatsu S, Suga Y, Kon J, Matsuba S, Hashimoto Y, Ogawa H. A Japanese patient with a mild form of lamellar ichthyosis harboring two missense mutations in a core domain of the transglutaminase 1 gene. Br J Dermatol 2004; 150: 390-2.

14 Raghunath M, Hennies HC, Ahvazi B, Vogel M, Reis A, Steinert PM, Traupe H. Self- healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. J Invest Dermatol 2003; 120: 224-8.