Ichthyosis lamellar

A. P. M. Lavrijsen, J. A. Bouwstra, G. S. Gooris, A. Weerheim, H. E. Bodde, and M. Ponec. Reduced skin barrier function parallels abnormal stratum comeum lipid organization in patients with lamellar ichthyosis. J. Invest. Dermatol. 105 619-624 (1995). 

There are several genetic skin diseases with known defects in the lipid metabolism. Atopic dermatitis, lamellar ichthyosis, and psoriasis have been the most widely studied with respect to epidermal barrier function and alterations in the lipid profile. Deviations in the lipid profile have been linked with an impaired stratum corneum barrier function. Atopic dermatitis is characterized by inflammatory, dry and easily irritable skin, and overall reduced ceramide levels in the stratum corneum [58-60]. In particular a significant decrease in the ceramide 1 level is observed, whereas the levels of oleate that is esterified to ceramide 1 are elevated [59]. Both aberrations may be responsible for the reduced order of the lamellar phases as observed with freeze fracture electron microscopy [61]. It has further been established that, in comparison to healthy stratum corneum, the fraction of lipids forming a hexagonal packing is increased [61]. A recent study reveals that the level of free fatty acids... 

Huber, M., et al. 1995. Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267 525. 

Pilgram, G.S.K., et al. 2001. Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis. J Invest Dermatol 117 710. 

An accumulation of scales on the skin surface may be due to either an increased production of corneocytes, such as in psoriasis, or to a delayed desquamation. It may be predicted that conditions with delayed desquamation, once their pathophysiology on the molecular level is understood, will be highly informative with regard to the understanding of desquamation. Two such conditions are recessive X-linked ichthyosis (RXI) and lamellar ichthyosis. 

Parmentier, L., Blanchet-Bardon, C., Nguyen, S., Prud homme, J.-F., Dubertret, L., and Weissenbach, J., Autosomal recessive lamellar ichthyosis identification of a new mutation in transglutaminase 1 and evidence for genetic heterogeneity, Hum. Mol. Genet., 4, 1391, 1995. 

Huber, M., Rettler, I., Bernasconi, K., Wyss, M., and Hohl, D., Lamellar ichthyosis is genetically heterogenous — cases with normal keratinocyte transglutaminase, J. Invest. Dermatol., 105, 653, 1995. 

X-linked Ichthyosis Sjogren - Larsson Lamellar Ichthyosis Vohwinkel syndrome I. Bullosa Siemens Epidermolytic PPK Pachonychia congen EHK (I. Bullosa) Palmopl. Keratoderma GABEB... 

The two most severe types of ichthyosis, lamellar ichthyosis (LI) and epidermolytic hyperkeratosis (EHK), are distinct families of diseases with completely different etiologies (see Figure 8.1 and Table 8.3). Nevertheless, LI and EHK have several things in common they are rare, congenital diseases (prevalence <1/100,000) with more or less generalized hyperkeratosis and a defective skin barrier, and they usually demands vigorous therapy. 

Ichthyosis vulgaris X-Linked ichthyosis Lamellar ichthyosis (nonbullous ichthyosiform erythroderma) Epidermolytic hyperkeratosis (bullous ichthyosis)... 

FIGURE 8.5 Patient with lamellar Ichthyosis (due to TGM1 mutations) who twice daily for 2 mo. received a cream formulation containing lactic acid (5%) and propylene glycol (20%) on the right arm as compared to on the left arm (Reproduced from. ..31)... 

Ganemo, A., Virtanen, M., and Vahlquist, A., Improved topical treatment of lamellar ichthyosis a double-blind study of four different cream mixtures, Br. J. Dermatol., 141, 1027, 1999. 

Stege, H., Hofmann, B., Ruzicka, T., and Lehmann, P, Topical application of tazarotene in the treatment of nonerythrodermic lamellar ichthyosis, Arch. Dermatol., 134, 640, 1998. 

Redondo, P. and Bauza, A., Topical N-acetylcysteine for lamellar ichthyosis, Lancet, 354, 1880, 1999. 

Kiistala, R., Lauharanta, J., and Kanerva, L., Transepidermal water loss and sweat gland response in lamellar ichthyosis before and during treatment with etretinate report of three cases, Acta Derm. 

Recently, the skin barrier properties and SC structure of patients with autosomal recessive lamellar ichthyosis have been examined relative to healthy volunteers (Lavrijsen et al., 1995). Barrier function was found to be impaired, and SC lipid structure was observed to be remarkably different. Normal SC had a repeat period of 64 A, whereas the diseased SC had values between 50 and 59 A. 

These findings imply that there must be another explanation for the parakeratosis found in psoriasis aside from the increased cell division, decreased transit time, and lack of time necessary for dissolution of the nucleus to take place. Comparable findings, i.e., increased cell proliferation without parakeratosis, have been reported by Frost et al. in congenital lamellar ichthyosis (F20) and by Kurban and Azar in familial continual skin peeling (K8). One explanation which has been advanced is that the DNA is chemically altered or more firmly bound to protein since, according to Jarrett and Spearman (J3) and Steigleder et al. (S21), it is not as easily digested by DNase as is normal DNA. 

Peck, G.L. and Yoder, F.W. (1976) Treatment of lamellar ichthyosis and other keratinising dermatoses with an oral synthetic retinoid. Lancet, 2, 1172-1174. 

It may at first appear paradoxical that diseases such as psoriasis and lamellar ichthyosis, which are characterized by a hyperproliferative epidermis, can benefit from dmgs such as the retinoids, which can stimulate epidermal proliferation under certain experimental conditions. However, when tested in patients with psoriasis, etretinate led to decreased ornithine decarboxylase activity, decreased levels of urinary and cutaneous polyamines, and decreased epidermal DNA synthesis (Kaplan et al., 1983). 

Fig. 5. Generalized lamellar ichthyosis prior to treatment with isotretinoin. [Reprinted with permission from Peck and Yoder (1976).]...

In addition to reduction in scale, patients with lamellar ichthyosis treated with retinoids also notice increased heat tolerance and ability to sweat and improved ectropion (Baden et al., 1982). Clearing in these patients is usually not complete and may be greater in the summer than in the winter. 

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