Type IV of
hypersensitivity reaction is usually manifested in the skin in different clinical pattern. According to traditional Gell and Coombs classification, the mechanism of IV type of
allergic reaction has been associated with contact
allergy with the activity of lymphocytes Th1 secreting
interferon gamma. Now, this vision seems to be too simplified. In the last years there were publications, which can throw a new light on these complicated mechanisms leading to the development of the type IV of
allergy, especially to drugs,
nickel and other
haptens and also can explain the differentiation of clinical pattern in respective patients. The skin symptoms in type IV of
hypersensitivity are triggered by activation of specific T-cell CD4+ and CD8+. Immunohistochemical and functional analysis of reactive T-cell has shown that the
delayed hypersensitivity reaction depends on the secreted
cytokines. For example maculo-papular
exanthema may be either triggered by Th1 or Th2 in nature and
cytokines interferon gamma,
tumor necrosis factor alfa or
interleukin-4, 5 and 13. Bullous reactions (i.e. Stevens-Johnsons Syndrome or
toxic epidermal necrolysis) are characterized by widespread keratinocyte apoptosis, a consequence of high CD8+ T-cell involvement and the molecular cytotoxicity of Fas,
perforin and
granzyme B. Pustular
exanthema reactions are stimulated via the T-cell release of 11-8 and granulocyte-monocyte colony-stimulatig factor (
GM-CSF). For the better understanding of these inflammatory cascades deleted type IV of
hypersensitivity reactions have been re-classified into four main subtypes: 1. IVa with Th1 and monocyte directed and
cytokines: IFNgamma,
IL-1,
IL-2, 2. IVb with Th2 and eosinophils directed and
cytokines: L-5,
IL-4,
IL-13, 3. IVc with T CD8+ directed and
cytokines:
perforin, granzyme B,
Fas Ligand, 4. IVd with T CD4+, CD8+ and neutrophil directed and
cytokines:
IL8,
GM-CSF. Clinically
delayed hypersensitivity eruptions are often an overlap of
cytokine pathways, with one preferential reaction dominating the final picture. Type IVa and IVc play a role inthe mechanism of
contact dermatitis, however type IV b in chronic
asthma, chronic
allergic rhinitis and maculo-papular
exanthema with
eosinophilia, type IV c in bullous reactions (i.e. Stevens-Johnsons Syndrome or
toxic epidermal necrolysis), so type IV d in pustular
exanthema reactions (i.g. AGEP - Acute Generalized Exanthematosus Pustule,
Behcet disease). This different clinical pattern of allergic disease mainly including
drug allergy to
nickel and other
haptens as well as chronic
asthma and
allergic rhinitis may be explained by above mechanisms. The study of different mechanisms of four subtypes of type IVof
allergic reaction may be helpful in the differential diagnostics and in the treatment of allergic diseases.