The large number of already known genetic causes of dermatological diseases could lead to the conclusion that in the future diagnoses will be made by genetic analysis alone. However, the Pediatrics Workshop at the International Summer Academy in Munich emphasized the still valid importance of clinical diagnostics and the clinical view.
Hereditary keratinization disorders are a clinically and genetically heterogeneous group of skin diseases. A consensus conference on hereditary ichthyoses was held in 2009, and more than 36 entities were described, named, and classified into subtypes. MeDOC (“Mendelian Disorders of Cornification”) defines hereditary ichthyoses as “genetic disorders characterized by hyperkeratosis and scaling of the entire skin.” Palmoplantar keratodermatoses may occur in association with ichthyoses or in isolation [1]. Other disorders of the form include porokeratosis, pytiriasis rubra pilaris (PRP), Darier’s disease, and related disorders [2].
Every classical diagnostic algorithm starts with the description of the phenotype, emphasized PD Dr. med. Vincenz Oji from Münster. Age at onset, initial clinical signs and course, and involvement of other organs provide important initial clues. Familial occurrence and mode of inheritance provide further pieces of the mosaic. Skin biopsy is still important for morphological and functional analysis. Only in fourth place did Dr. Oji list molecular genetic and mutation analyses. They are still not always possible, often not necessary, and unwanted by the patient, according to his current assessment.
Ichthyosis vulgaris is caused by a nonsense mutation in the filaggrin gene, the mode of inheritance is autosomal semi-dominant. The prevalence is reported to be 1:250-400. Hyperlinearity of the palms is almost always present. Recessive x-linked ichthyosis (RXLI) affects only male offspring. “Other subtypes of congenital ichthyoses are very rare, and the care of these orphan diseases is complex and requires specialized centers,” Dr. Oji emphasized. A special form of congenital isolated ichthyosis is self-healing collodion baby (SICI). The newborn is covered with a collodion-like membrane at birth. A few days or weeks postnatally, the skin appearance then completely normalizes. “This statement can help parents with a collodion baby during the difficult first time,” Dr. Oji said.
Topical ureas, acetylsalicylic acid, and retinoids are options in therapy. Macrogol shows a very good effect. Systemic retinoids reduce scaling and skin thickening and promote the ability to sweat. Adalimumab may be used in Netherton syndrome (off-label). As a bath additive, baking soda (sodium hydrogen carbonate) has proven to be effective, which leads to the denaturation of keratin and has a dandruff-dissolving effect via alkalization. Rice, corn and wheat starch can also be considered as alternative bath additives.
Photodermatoses in children
Children should be effectively protected from sun damage, unfortunately prophylaxis is still not practiced enough. “When summer begins, we see children and adolescents in the hospital again and again with severe symptoms of sunburn,” reported Prof. Percy Lehmann, MD, Düsseldorf. He described why the diagnosis of light dermatoses can be problematic. Many subtypes flare only briefly such as solar urticaria [3]. Light dermatoses are based on a qualitatively abnormal reaction to solar (mostly UV) radiation. Idiopathic photodermatoses with unknown photosensitizer are distinguished from phototoxic and -allergic reactions in which the (photo-)sensitizing substance is known. The anamnesis is decisive for the diagnosis. In addition, test areas can be repeatedly checked or irradiated. Through this experimental provocation, the skin changes should be reproducible, Prof. Lehmann explained.
There are rare photodermatoses, such as hydroa vacciniformia (prevalence 0.34/100,000), but also very common ones, such as polymorphous light dermatosis PLD (prevalence 10-20%). PLD is more common in females and may be papular, plaque-like, or papulovesicular. Hydroa vacciniformia is associated with Epstein-Barr virus (EBV). Important differential diagnoses include photoallergic eczema, ictus, and prurigo simplex, as well as delayed-type light urticaria, erythema multiforme, and lupus erythematosus.
Normally, PLD heals on its own after some time. However, those affected must avoid the sun or cover the respective skin areas. Healing can be accelerated with topical corticosteroids. Against the itching it helps to cool the spots or also to take antihistamines. In the further course of sun exposure, those affected then usually show a habituation effect, so that eventually even stronger UV radiation is tolerated. If PLD is known, phototherapy can be used to harden the skin as a preventative measure before the vacation. “However, UV exposure should be done by a dermatologist and not on your own in a solarium,” Prof. Lehmann emphasized. It is crucial to educate the patient about cautious light acclimation at the beginning of seasonal sun exposure and to use broad-spectrum, high SPF sunscreens.
Do you know the Ambras syndrome?
Prof. Eli Sprecher, MD, Tel Aviv, gave an overview of the genetics of congenital hyper- and hypotrichosis. Numerous diseases with sounding names like “Ambras syndrome”, “generalized congenital hypertrichosis x-linked”, “Cantu syndrome”, “Marie Unna hypotrichosis” or “autosomal recessive Naxos syndrome” are mainly familiar to experts. Most of these syndromes are gaze diagnoses for them based on phenotype, and the underlying mutations are often already well known. In H syndrome (localized hypertrichosis), for example, mutations are present in the nucleoside transporter gene, which in addition to the hair growth disorder can also lead to other symptoms such as heart abnormalities or hearing loss. In ANE syndrome (Alopecia, Neurological defects, Endocrinopathy), a genetic defect leads to a disorder in the biogenesis of ribosomes (ribosomopathies) [4]. There is great interest in her research results, Prof. Sprecher told us, because, for example, new epilation methods based on the discovered mechanisms of alopecia are conceivable.
Underlying the hair shaft abnormalities with increased hair fragility such as monilethrix, trichorrhexis nodosa, trichorhexis invaginata, pili torti, and bamboo hair in Netherton syndrome are known mutations for hair keratin. In the algorithm that Prof. Sprecher showed for hypotrichosis clarification, all fields with associated mutations are already filled in.
Eczema herpeticatum
Eczema herpeticatum (EH) as an acute, disseminated, large-scale herpes simplex virus infection is still a feared complication of eczematous skin diseases, especially atopic eczema. The clinical picture, which appears as a vesiculoerosive eruption, is often accompanied by severe general symptoms and fever; HSV keratitis, encephalitis, and pneumonia are particularly severe. Andreas Wollenberg, MD, from Munich, Germany, gave an update at ISA on this infection with HSV, which often presents with dramatic-looking clinical pictures, mostly type I, rarely type II.
A complex interplay of different factors seems to be causative for the pathogenesis of eczema herpeticatum, with eczema-related unmasking of binding sites for HSV, lack of upregulation of antiviral peptides, and a deficiency of plasmacytoid dendritic cells being pathogenetically relevant. Why some neurodermatitis patients get an EH several times and others never, on the other hand, has not been conclusively clarified. HSV lesions are preferentially found in AD-affected regions. Patients with early onset, severe or untreated atopic eczema have a higher incidence of the disease. EH patients have more atopic comorbidities, almost all of intrinsic character.
Therapy of choice is systemic aciclovir therapy: p.o. 400 mg 5× daily, i.v. 5-10 mg/kg per dose tid. Valaciclovir (500 mg tid) and famciclovir (250 mg tid) have the advantage of single administration. As a tip, Prof. Wollenberg mentioned the following: Methylprednisolone 0.5 mg/kg/d accelerates healing with systemic therapy. In severe cases or ocular involvement, interferon-alpha 2b is an option.
Source:3rd Munich International Summer Academy of Practical Dermatology ISA, July 21-26, 2013, Munich.
Literature:
- Oji V: Clinical presentation and etiology of ichthyoses. Overview of the new nomenclature and classification. Dermatologist 2010 Oct; 61(10): 891-902.
- Schmuth M, et al: Inherited ichthyoses/generalized Mendelian disorders of cornification. Eur J Hum Genet 2013 Feb; 21(2): 123-33.
- Lehmann P, Schwarz T: Photodermatoses: diagnosis and treatment. Dtsch Arztebl Int 2011; 108(9): 135-41.
- Nousbeck J et al: Alopecia, Neurological Defects, and Endocrinopathy Syndrome Caused by Decreased Expression of RBM28, a Nucleolar Protein Associated with Ribosome Biogenesis. Am J Hum Genet 2008 May 9; 82(5): 1114-1121.
DERMATOLOGY PRACTICE 2013; (23)6: 24-26
