Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity. OBJECTIVES: To evaluate further the potential role of certain cytokines and chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN and to establish whether such diseases are polarized preferentially towards a T-helper (Th) 1 or Th2 pattern. METHODS: Biopsy specimens from eight patients with EM, six with SJS/TEN and three healthy controls were stained for immunohistochemical examination using the alkaline phosphatase-antialkaline phosphatase method. The monoclonal antibodies used included those to tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-5, IL-13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3) and CXCR4. RESULTS: The SJS/TEN specimens showed significantly higher expression of all the cytokines and chemokine receptors (except CXCR3) tested than the EM specimens. Both lesional series showed significantly higher expression of all the receptors tested than the healthy control specimens, with the sole exception of a lower expression of CCR3 in EM specimens. Comparison between molecules associated with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no significant imbalance between Th1 and Th2 in SJS/TEN. CONCLUSIONS: We have provided further evidence that TNF-alpha is strongly expressed in SJS/TEN lesions and therefore it may be involved in the epidermal necrosis featured in such diseases. IFN-gamma may play an important role both in EM and SJS/TEN. IL-2, IL-5 and IL-13 may contribute to the cutaneous immunoinflammation in these diseases. Chemokine receptors may be involved strongly in the recruitment of inflammatory cells in lesional skin. In our cases we found a sharp polarization towards a Th1 pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern.

The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.

BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. OBJECTIVES: To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN. METHODS: Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase. RESULTS: The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+ macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+ cells in SJS/TEN but much fewer in EM. CONCLUSIONS: Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism.

Clinical and immunohistochemical study of the effect of a cosmetic product in patients with asteatotic eczema.

Cutaneous xerosis is a common clinical condition associated with an altered barrier function of the stratum corneum. Xerotic skin appears dry, rough and slightly scaling. Patients complain of pruritus and stinging. Our aim was to investigate the clinical effects of a cosmetic ointment (Scherilan) in patients with circumscribed senile xerosis (also called asteatotic eczema). Moreover, variations in expression of epidermal proteins such as keratin (K)-5 and involucrin, detected by immunohistochemistry, were also evaluated before and after topical treatment. We enrolled 30 patients (11 males, 19 females) with asteatotic eczema. We examined dryness, roughness and desquamation and symptoms such as itching and dryness. A score of 0 to 3 was assigned to each of these parameters. A biopsy was performed in seven patients before and after a 21-day topical treatment. All skin specimens were then immunostained with antibodies to K5 and involucrin. At day 7 or 21 of treatment all signs of xerosis and pruritus were significantly reduced; furthermore, the reduction increased with the duration of therapy. Before treatment K5 was strongly expressed in stratum basale (SB) and stratum spinosum (SS), while involucrin was strongly expressed in stratum granulosum (SG) and the upper portion of SS. In contrast, after treatment immunostaining for K5 was restricted to SB and the lower part of SS, while involucrin showed intense staining in SG. We highlight the importance of treating cutaneous xerosis with an ointment such as this one, which probably induces an increase of lipid content of the SC intercellular matrix.