The skin is a dynamic interface of trafficking immune cells that may remain localised and respond to nearby stimuli, or migrate through the skin in response to more distant triggers. The skin has been called ‘the immunological battleground of the body’ and immune cells involved in inflammatory reactions may be part of a local immune reaction or migrate to the skin as a result of antigenic stimuli at distant sites. Malfunction of the sophisticated human immune system may result in the body attacking its own tissues, that is, failure to distinguish ‘self’ from ‘non-self’. These autoimmune responses may develop against a tissue in a specific organ such as the thyroid gland, or to tissues within and between organs resulting in connective tissue diseases.

Connective tissue disease can be difficult to define but encompasses disorders that involve tissues connecting and surrounding organs.

Connective tissues include the extracellular matrix and support proteins such as collagen and elastin. Acquired disorders of connective tissue are thought to have an autoimmune basis, many of which have distinctive clinical features and patterns in laboratory investigations. However, at times classification may not be easy. What triggers dysregulation of the immune system is usually unknown; however, some recognised factors include sunlight, infections and medication. Patients may have an underlying hereditary susceptibility to develop autoimmune diseases, marked by specific HLA (human lymphocyte antigen) types in some cases.

In autoimmune disorders immune cells may be attracted to particular targets within the skin locally (pemphigus and pemphigoid—Chapter 8) or accumulate at sites of connective tissues in multiple organs (systemic lupus erythematosus (SLE) and dermatomyositis). Once at their destination these immune cells trigger a cascade of chemical messages leading to inflammation.

The possibility of an underlying connective tissue disorder should be considered if a patient complains of any combination of symptoms including cutaneous lesions (especially face and fingers), joint pains, muscle aches, malaise, weakness, photosensitivity, Raynaud’s phenomenon and alopecia. Linking the clinical symptoms and signs with the most appropriate investigations in order to arrive at a unifying diagnosis is a challenge to even the most experienced medical practitioner (Box 9.1).

Complex reactions occurring specifically in the capillaries and arterioles of the skin may lead to cutaneous erythema (redness). The erythema may be macular or papular and may be transient or last for weeks. Blood vessels can become leaky, leading to pouring out (extravasation) of red blood cells into the tissue with or without inflammation of the blood vessel walls. Inflammation of blood vessel walls is called vasculitis and may involve arteries and/or veins. Vasculitis can also lead to stenosis, occlusion and ischaemia.

PAN is a systemic vasculitis of small- to medium-sized arterioles that most commonly affects the skin and joints. Immune complexes mediate the disease, activating the complement cascade leading to inflammatory damage to vessels. The sites of blood vessel bifurcation are commonly affected and this leads to micro-aneurysm formation with resultant occlusion and haemorrhage. ANCA may be positive. Patients present with general malaise, fever, weight loss, weakness, arthralgia, neuropathies and skin lesions. Of the patients, 60% develop renal involvement, which may lead to renal failure. Cutaneous manifestations may include a subtle lacy/mottled pattern (livedo reticularis), purpura, tender subcutaneous nodules, ulceration and necrosis, particularly on the lower limbs. Investigations may include angiography and tissue biopsy (skin, sural nerve or muscle). Management relies on oral steroids with the addition of cyclophosphamide in severe cases.

This usually occurs in children (75% of cases) or young adults (M > F); the aetiology is unknown, but up to 50% of patients have preceding upper respiratory tract symptoms and a positive antistreptolysin O titre (ASOT). The skin, kidneys (IgA nephropathy), GI tract and joints are mainly affected. IgA, complement and immune complexes are deposited in small vessels (arterioles, capillaries, venules), leading to systemic vasculitis. HSP is characterised by a vasculitic rash on the buttocks and lower legs (which may associated with oedema of scrotum/hands/ears), abdominal pain and vomiting, joint pains in the knees/ankles and haematuria. Skin/renal biopsy may demonstrate deposition of IgA on immunofluorescence, which can support the diagnosis. Treatment is mainly supportive and most patients recover within weeks. Occasionally, the condition can persist and systemic corticosteroids have been used to treat skin, gastrointestinal and arthritis symptoms but steroids have not been shown to prevent or treat renal disease.