Annular Lichenoid Dermatitis (of Youth)

About 20 years after its first description, Annular Lichenoid Dermatitis of Youth (ALDY) is recognized as a distinctive lichenoid dermatosis with specific clinical and histological features. The disease occurs mostly in young persons all over the world, runs a chronic course, and has an obscure etiopathogenesis. Clinically, lesions consist of persistent, asymptomatic erythematous macules and round-oval annular patches with a red-violaceous non-scaling border and central hypopigmentation, mostly localized on the groin and flanks. Histology shows a peculiar lichenoid dermatitis characterized by irregular epidermal hyperplasia with an alternation of thinned and quadrangular rete ridges and a dense band-like lichenoid infiltrate of lymphocytes in the papillary dermis. Typically, there is infiltration of lymphocytes into the lower epidermal layers with massive necrosis/apoptosis of keratinocytes, which is limited to the tips of rete ridges. Dermal lymphocytes are usually CD3+, CD4+, while most of the intraepidermal T cells are CD8+. Analysis of TCR-γ-chain gene rearrangement displayed polyclonality in all cases examined. Differential diagnosis mainly includes morphea, mycosis fungoides, annular erythemas and inflammatory lesions of vitiligo. Topical corticosteroids and topical tacrolimus represent the most effective drugs for ALDY treatment.

“Tineariasis” (or plaque-psoriasis induced by Terbinafine)

Terbinafine is an anti fungal drug used worldwide to treat dermatophytosis. Although generally is well tolerated, several cutaneous side effects have been described. One of them is the induction or exacerbation of psoriasis, especially the pustular type. We describe a case of plaque-psoriasis induced by terbinafine in a young patient. Skin biopsy was performed to confirm the diagnosis and the suspected drug was discontinued. Biopsy showed regular epidermal hyperplasia with parakeratoses and neutrophils in the corneal layer. No fungal elements were observed. Improvement was observed after discontinuation of terbinafine. We present a new case of the induction of plaque-psoriasis after the use of oral terbinafine and conclude that this drug should be used with caution in predisposed patients. Keywords: psoriasis; pustular posriasis; plaque-psoriasis; terbinafine

Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas

ALCL is a tumor of activated T cells and possibly innate lymphoid cells with several subtypes according to clinical presentation and genetic lesions. On one hand, the expression of transcription factors and cytokine receptors triggers signaling pathways. On the other hand, ALCL tumor cells also produce many proteins including chemokines, cytokines and growth factors that affect patient symptoms. Examples are accumulation of granulocytes stimulated by IL-8, IL-17, IL-9 and IL-13; epidermal hyperplasia and psoriasis-like skin lesions due to IL-22; and fever and weight loss in response to IL-6 and IFN-γ. In this review, we focus on the biology of the main ALCL subtypes as the identification of signaling pathways and ALCL-derived cytokines offers opportunities for targeted therapies.

Condyloma latum of the plantar foot: Case report of an unusual manifestation of secondary syphilis

Condyloma lata, a cutaneous manifestation of secondary syphilis, typically presents as verrucous papules or plaques in the anogenital area. Here, we present a case of secondary syphilis presenting in a 38-year-old man as condyloma latum of the plantar foot in the absence of other cutaneous findings of secondary syphilis. The plantar foot is an unusual location for condyloma lata which has not previously been reported in the medical literature. Histopathology was essential to diagnosis in this case and demonstrated verrucous epidermal hyperplasia with a plasma cell-rich infiltrate in the dermis and innumerable spirochetes in the epidermis. The patient was successfully treated with intramuscular penicillin benzathine G. Given the recent rise in the incidence of primary and secondary syphilis, it is essential for clinicians to be aware of atypical presentations of secondary syphilis to avoid delays in treatment and decrease the risk of transmission to sexual partners.

Pterostilbene Supplementation Inhibits Early Inflammatory Response and Oxidative Stress in UVB-Induced BALB/C Mice

Extended dermal exposure of ultraviolet B (UVB) can induce erythema, hyperpigmentation, epidermal hyperplasia and cancer. Natural active compound such as pterostilbene (PS) is a potential UV-protecting agent as it has broad biological activities. This study aimed to evaluate the photoprotective effect of pterostilbene on ultraviolet-B-induced BALB/c mice. Twenty-four female mice were randomised into four groups (n=6/group): vehicle control (VC); UVB irradiated only (UVB only); UVB irradiation treated with pterostilbene 10 mg/kg (PS10+UVB); (iv) UVB irradiation treated with pterostilbene 20 mg/kg (PS20+UVB). The PS treatments were given for 14 days, and UVB was given at dose 250 mJ/cm2 on days 9, 11, and 13 of the treatment periods. The results showed that PS lessened redness and scaling on the skin of UVB-irradiated mice. The skinfold thickness and epidermal thickness in the PS-treated group were significantly reduced (p<0.05) in comparison with those in the UVB only group. The PS10 and PS20 groups (5.927 ± 0.354 and 5.660 ± 0.765 nmol/g, respectively) demonstrated significantly decreased MDA levels (P<0.05) relative to the UVB only group (13.343 ± 1.350 nmol/g). The GSH level in both PS10 (0.555 ± 0.020 µmol/mg) and PS20 (0.568 ± 0.055 µmol/mg) groups increased significantly (p<0.05) compared with that in the UVB only group (0.376 ± 0.025 µmol/mg). SOD activity in the PS20 group (1.388 ± 0.172 U/min/mg) increased significantly (p<0.05) compared with that in the UVB only group (0.561 ± 0.034 U/min/mg). Histological observation showed that PS reduced leukocyte infiltration and epidermal hyperplasia. Hence, oral PS may exert a photoprotective effect by acting as an anti-inflammatory and antioxidant agent on UVB-irradiated mice skin.

MLL4 is a critical mediator of differentiation and ferroptosis in the epidermis

The epigenetic regulator, MLL4 (KMT2D), has been described as an essential gene in both humans and mice. In addition, it is one of the most commonly mutated genes in all of cancer biology. Here, we identify a critical role for Mll4 in the promotion of epidermal differentiation and ferroptosis, a key mechanism of tumor suppression. Mice lacking epidermal Mll4, but not the related enzyme Mll3 (Kmt2c), display features of impaired differentiation and human pre-cancerous neoplasms, including epidermal hyperplasia, atypical keratinocytes, and a loss of polarization, all of which progress with age. Mll4 deficiency profoundly alters epidermal gene expression, and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, Aloxe3). Beyond identifying a novel role for Mll4-mediated tumor suppression in the skin, our data reveal a potentially much more broad and general role for ferroptosis in the process of epidermal differentiation and skin homeostasis.