The key role of aquaporin 3 and aquaporin 10 in the pathogenesis of pompholyx.

Pompholyx remains a chronic skin affliction without a compelling pathophysiological explanation. The disease is characterized by the sudden onset of vesicles exclusively in the palms and soles which generally resolves. However, the disease may progress and the vesicles may expand and fuse; with chronicity there is deep fissuring. Multiple therapeutic approaches are available, but the disease is often resistant to conventional treatments. Currently, oral alitretinoin is used for patients with resistant chronic disease; however, this therapy is only approved for use in the UK, Europe and Canada. In this paper we wish to put forward a hypothesis: exposure to water and the subsequent steep osmotic gradient imbalance are key factors driving skin dehydration seen in pompholyx patients once the disease becomes chronic. The mechanistic explanation for the epidermal fissuring might lie in the over-expression across the mid and upper epidermis, including the stratum corneum, of two water/glycerol channel proteins aquaporin 3 and aquaporin 10, expressed in the keratinocytes of afflicted pompholyx patients. The over-expression of these two aquaporins may bridge the abundantly hydrated dermis and basal epidermis to the outer environment allowing cutaneous water and glycerol to flow outward. The beneficial effects reported in alitretinoin-treated patients with chronic hand eczemas may be due potential regulation of aquaporin 3 and aquaporin 10 by alitretinoin.

The role of patch testing for chemical and protein allergens in atopic dermatitis.

Many patients who present for evaluation of allergic contact dermatitis have an atopic diathesis. Although the immunologic basis of atopic dermatitis differs from that of allergic contact dermatitis--and patients with atopic dermatitis are less easily sensitized under experimental conditions--atopic patients do develop allergic contact dermatitis, and patch testing is a valuable part of their medical care. Delayed (7-day) patch test readings are especially important in atopic patients to distinguish allergy from irritancy and to evaluate for steroid allergy. The utility of atopy patch tests to aeroallergens such as dust mite is increasingly recognized; aeroallergens may be the cause of a type of protein contact dermatitis.

Diagnosis and treatment of allergic skin disorders in the elderly.

Allergic skin disorders in the elderly may arise from contact with or ingestion of offending allergens. Itching associated with skin allergy must be distinguished from other causes of itching in the elderly such as xerosis, itching due to systemic disease and bullous disease. Although elderly people have somewhat decreased cell-mediated immunity and may be harder to sensitise under experimental conditions, they have had many years to acquire allergic responses, and therefore develop contact dermatitis frequently. Patch testing is a valuable tool to diagnose contact allergy and should be used often in the elderly, particularly in patients at high risk of contact dermatitis, such as those with chronic lower extremity dermatitis or ulcers due to venous stasis. When prescribing topical medications to high risk patients, a knowledge of the common sensitisers is important. In addition to allergy to medicaments and dressings used to treat stasis ulcers, contact allergy to dental prostheses and medications used to treat ocular disease are common in the elderly as a result of increased usage and exposure. Rash caused by ingested allergens is much more commonly due to medications than to food in the elderly. Allergic noneczematous dermatoses in the elderly are commonly drug-induced. Urticarial skin reactions are often associated with the administration of antibacterials, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants or opioids. Morbilliform rashes are a common sign of systemic reaction to anticonvulsants, gold, allopurinol or diuretics. Phototoxic reactions may be associated with the administration of tetracyclines, diuretics, NSAIDs and antihyperglycaemic agents. Patient-specific variables such as HLA type and concomitant medication may affect the likelihood of an allergic response to medication. Many elderly patients take multiple medications, which can make diagnosis of drug allergy difficult because diagnosis is most commonly accomplished by observing clinical response once the medication is withdrawn. In the case of lichenoid cutaneous reactions, clinical improvement may take several months after withdrawal of the offending drug. Laboratory tests to detect drug-induced allergic skin disorders may be available in the future.

Cell cycle analysis by flow cytometry of non-exposed, sun-exposed, and tretinoin-treated skin.

The percentage of keratinocytes in the proliferative phase of the cell cycle (S + G2 + M) was measured by DNA flow cytometry in sun-exposed, non-exposed, and tretinoin-treated skin. Before tretinoin treatment, the percentage of keratinocytes actively cycling was higher in sun-exposed than in non-sun-exposed skin (p = .002) and was correlated with clinically assessed photodamage (p = .007). Subsequently, tretinoin-treated sun-exposed skin was compared to the pre-treatment sun-exposed skin. Overall, there was no statistically significant change. However, there was a trend toward a decrease in the percentage of keratinocytes in the S + G2 + M phases immediately after four months of tretinoin use that was limited to the most severely damaged patients. This effect was no longer evident two months after discontinuing treatment. This is the first study, to our knowledge, utilizing flow cytometry to investigate the effects of tretinoin in patients with varying degrees of photodamage.

Rosacea-like lesions due to familial Mycobacterium avium-intracellulare infection.

Mycobacterium avium-intracellulare (MAI) is a non-tuberculous, nonlepromatous or "atypical" mycobacterium now seen frequently in patients with acquired immunodeficiency syndrome (AIDS). In the past decade, the incidence appears to have increased in non-AIDS patients. Although cutaneous involvement is rare, two brothers without detectable immune defects who both presented with cutaneous MAI infection are described; the older brother also has disseminated disease. The cutaneous presentation of MAI, as well as immune and genetic defects that may predispose to mycobacterial infection, are discussed.