Systemic immunodeficiency is known to facilitate the onset of opportunistic infections, tumours and immune disorders in any district of the body. There are clinical events, such as chronic lymphoedema, herpetic infections, vaccinations and heterogeneous physical injuries which can selectively damage and immunologically mark the cutaneous district they act upon. After the causing event has disappeared, the affected district may appear clinically normal, but its immune behaviour is often compromised forever. An immunocompromised district becomes a site which is particularly susceptible to subsequent outbreaks of opportunistic infections, tumours and immune disorders confined to the district itself. In this review, there is an ample case-report collection of opportunistic disorders (infectious, neoplastic, immune) which appeared in immunocompromised districts. The cases have been grouped according to the clinical settings responsible for the local immune imbalance: regional chronic lymphoedema; herpes-infected sites, which feature the well-known Wolf's isotopic response; and otherwise damaged areas, comprising sites of vaccination, ionizing or UV radiation, thermal burns and traumas. Whatever the immunocompromising factor, a common denominator which facilitates the occurrence of tumours, infections and dysimmune reactions in an immunocompromised district may reside in locally hampered lymph drainage and/or locally altered neuromediator signalling. In fact, any obstacle to the normal trafficking of immunocompetent cells through lymphatic channels or any interference with the signals that the neuropeptides and neurotransmitters released by peripheral nerves send to cell membrane receptors of immunocompetent cells, can significantly alter the local immune response, thus paving the way for heterogeneous opportunistic disorders in the immunocompromised district.

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