Protein kinase D distribution in normal human epidermis, basal cell carcinoma and psoriasis.

BACKGROUND: Keratinocytes undergo a defined programme of proliferation and differentiation during normal stratification of the epidermis. Anomalies in the signalling pathways controlling this process probably contribute to the pathogenesis of hyperproliferative dermatological diseases, including psoriasis and basal cell carcinoma (BCC). We have previously proposed that protein kinase D (PKD) is a proproliferative signalling enzyme in keratinocytes and have speculated that abnormalities in its levels or regulation may contribute to hyperproliferative disorders of the skin. OBJECTIVES: To determine if hyperproliferative human skin disorders are characterized by abnormal protein expression or distribution of PKD, normal human epidermis was compared with BCC and uninvolved and involved psoriatic epidermis. METHODS: To examine protein expression, immunohistochemical analysis of human samples and Western blotting of neoplastic mouse keratinocytes was performed. Western analysis of neoplastic mouse cells using a phosphospecific PKD antibody allowed estimation of PKD activation status. RESULTS: Normal human epidermis demonstrated predominant PKD protein expression in the stratum basalis, the proliferative epidermal compartment, with decreased relative expression throughout the suprabasal strata. Uninvolved psoriatic skin showed a similar pattern, but in contrast, psoriatic lesions demonstrated a diffuse distribution of PKD staining throughout all strata. The majority of BCCs examined showed significant PKD protein levels and, in those biopsies in which the levels could be compared, elevated PKD levels relative to normal epidermis. PKD levels and activation status were also increased in a neoplastic mouse keratinocyte cell line. CONCLUSIONS: PKD was elevated or misdistributed in the hyperproliferative human skin disorders, BCC and psoriasis, as well as neoplastic mouse keratinocytes. We speculate that PKD exerts proproliferative and/or antidifferentiative effects in the epidermis, and that anomalous distribution and/or activation of PKD may be involved in precipitating or sustaining the disease process in BCC and psoriasis.

Mycosis fungoides bullosa: report of a case and review of the literature.

Mycosis fungoides, the most common type of cutaneous T-cell lymphoma, can manifest in a variety of clinical and histologic forms. Presentation with vesiculobullous lesions is extremely rare. We report the ninth documented case of mycosis fungoides bullosa in which other concomitant autoimmune blistering diseases were ruled out by negative immunofluorescence. All previously reported cases in the world literature since the first in 1887 are reviewed. We recommend the following defining criteria for the disease: (1) clinically apparent vesiculobullous lesions, with or without typical mycosis fungoides lesions (patches, plaques, tumors); (2) typical histologic features of mycosis fungoides (atypical lyphoid cells, epidermotropism, Pautrier's microabscesses) with intraepidermal or subepidermal blisters; (3) negative immunofluorescence (both direct and indirect, if possible) to rule out concomitant autoimmune bullous diseases; (4) negative evaluation for other possible causes of vesiculobullous lesions (eg, medications, bacterial or viral infection, porphyria, phototherapy).

Primary multiple miliary osteoma cutis and exogenous ochronosis.

Multiple miliary osteoma cutis (MMOC), a rare disorder characterized by the appearance of numerous bony nodules on the face, was initially classified as a consequence of severe, long-standing acne vulgaris. However, several cases have now been described in patients with no preceding history of acne or other inflammatory conditions. We report such a case of primary MMOC in a 75-year-old African American woman and highlight the differences between these conditions. We also note the incidental histologic finding of exogenous ochronosis, which, in our case, indicates the patient's use of hydroquinone-containing bleaching creams in an attempt to treat the disorder.

Effects of glycolic acid on light-induced skin pigmentation in Asian and caucasian subjects.

BACKGROUND: Topical use of alpha-hydroxy acid (AHA) may increase skin photosensitivity, as demonstrated by increased numbers of sunburst cells. However, effects of AHA on tanning have not been studied. OBJECTIVE: Our purpose was to study whether short-term use of glycolic acid hastens resolution of pre-existing light-induced pigmentation and whether the skin becomes tan more easily in Asian and Caucasian subjects after such treatment. METHODS: Six Asian and six Caucasian volunteers received separate irradiations of UVB and UVA to both sides of the lower back. In a double-blind fashion, patients then applied a 10% glycolic acid gel, pH 3.52, to one side of the back, including the irradiated area, and the contralateral extensor forearms once daily for 7 days and then twice daily for 2 weeks. A placebo gel, pH 5.75, was applied to the opposite sides. The subjects returned for measurement of residual tanning with a colorimeter and received additional irradiation to forearms and a second site on the back. Resulting pigmentation was measured immediately after irradiation, at 2 hours, and at 1 week. RESULTS: Increased UVB-induced skin tanning occurred on the forearm and the lower back in both races in areas pretreated with glycolic acid. UVA also caused increased tanning, but only on the extensor forearms in Asian subjects. Treatment with glycolic acid for 3 weeks had no effect on pre-existing light-induced pigmentation. CONCLUSION: Short-term topical treatment of glycolic acid caused an increase in UVB tanning as well as in UVA tanning in some subjects, even in the absence of overt irritation. The inclusion of UVB, and even UVA, sunscreen in AHA products may be warranted.

Ulcerated atrophic striae from etretinate.

Oral retinoids such as etretinate and acitretin are commonly associated with dose-dependent, mucocutaneous side effects such as dryness, peeling, and fragility. Although these effects can be extreme in some patients and even require discontinuation of treatment, thinning of skin to the point of atrophy and ulceration has never been reported in the English literature. We present the case of a patient with psoriasis in whom ulcerated atrophic striae developed during etretinate therapy. After discontinuation of etretinate, all cutaneous ulcers resolved. Subsequently, the patient had a favorable response to oral calcitriol (1,25-dihydroxy vitamin D3), a novel therapy for psoriasis.

Pemphigus foliaceus and renal cell carcinoma.

It is possible to distinguish the various forms of pemphigus from one another using clinical, histologic, and immunologic criteria. Paraneoplastic pemphigus, a recently defined type that is severe and often fatal, is associated with an underlying malignancy. We present the second reported case of pemphigus associated with renal cell carcinoma. We do not believe that either case represents paraneoplastic pemphigus, which suggests the possibility of some other link between these two diseases.

Leg ulcers: a common problem with sometimes uncommon etiologies.

In the U.S., leg ulcers present a significant clinical problem, occurring at a rate of approximately 600,000 new cases per year. In most cases, the cause of ulceration is venous or arterial in nature. One uncommon but significant cause of leg ulcers is sqaumous cell carcinoma (SCC). Although the incidence of SCC is higher in white than black populations, blacks with SCC typically exhibit involvement of areas of the skin that are not chronically sun-exposed, especially the lower extremeties. Predisposing factors include burn scars, chronic infection or ulceration, and chronic discoid lupus erythematosus. Leg ulcers of atypical presentation or those that fail to heal should alert the clinician to consider uncommon etiologies.