8.5 Urticarial syndromes

There are many dermatoses with an urticarial appearance. In contrast to “urticaria sensu strictu”, “urticarial syndromes” are not specific diagnoses, but they resemble skin lesions that look like wheals or hives. “Urticarial” refers to skin lesions that look like wheals, but are not.

Dermatoses that present with “urticaria-like” lesions include: insect bites (papular urticaria), acute dermatitis (early stage of contact dermatitis, atopic dermatitis), urticarial vasculitis (normo- and hypocomplementemic), urticaria pigmentosa (Darier`s sign in cutaneous mastocytosis), systemic infections (prodromal rash of viral infections), immunobullous diseases (e.g. premonitory pemphigoid, dermatitis herpetiformis), auto-inflammatory syndromes (e.g. CAPS; Schnitzler syndrome), neutrophilic dermatosis (e.g. Sweet syndrome), and autoimmune disorders (e.g. progesterone hypersensitivity).

A skin biopsy may be helpful in order to exclude other causative underlying dermatoses. There may be a normal or abnormal looking dermis with interstitial and/or peri-vascular edema, sometimes lymphocytic infiltrates or perivascular granulocytes with nuclear dust in the case of leucocytoclastic vasculitis. Depending on pathogenesis, eosinophils may be present.

The clinico-pathological correlation of lesions is nearly always essential for the diagnosis of urticarial syndromes. Urticaria is a clinical diagnosis made on the history and examination. For certain types, special diagnostic tools are necessary. In case of autoinflammatory syndromes, further investigations are required: C reactive protein, NLRP-3 genotyping in cryopyrin syndrome, high ferritin in adult Still`s disease, electrophoresis (immunoglobulin and paraproteins e.g IgM in Schnitzler Syndrome).

The main differential diagnosis is with Urticaria itself. Urticaria is an illness characterized by itchy wheals with or without angioedema, that can be acute or chronic (spontaneous or inducible). The differences between “Urticaria” and “urticarial” are as follows. In urticaria, wheals last for hours, itch is usually intense, are not scaly and never leave residual pigmentation. Urticaria is commonly associated with angioedema, fever is not present and rarely may show associated systemic disturbances e.g. arthralgias.

Different urticarial rashes have their own differential diagnosis.

Papular urticaria, also known as lichen urticatus, is the result of hypersensitivity to bites from certain insects. Itchy edematous papules and papulo-vesicles are usually excoriated. Histopathology: Epidermal intercellular and intracellular edema (spongiosis). Chronic dermal perivascular inflammatory infiltrate often extending to the deep dermis containing a significant admixture of eosinophils. Further investigations are not necessary.

Acute dermatitis. Macules, papules and vesicles. If macules coalesce, they form patches of erythema that may be edematous. Papules may coalesce to form plaques. Histopathology: Spongiotic microvesicles or macrovesicles with oozing in acute dermatitis. Showing acanthosis with parakeratosis in chronic dermatitis and a combination of both (subacute dermatitis). Further investigations: Patch testing, IgE sensitization.

Urticarial vasculitis. Recurrent episodes of urticarial lesions often associated with arthralgia and abdominal pain among other systemic symptoms. The individual lesions tend to persist 1 to 3 days and may result in purpura and hyperpigmentation. Histopathology: The dermis shows a leucocytoclastic vasculitis characterized by fibrinoid deposits in the blood vessel walls, and neutrophilic infiltrate with nuclear fragmentation (leukocytoclasia), and slight to moderate extravasation of erythrocytes.

Five types of cutaneous lesions in cutaneous mastocytosis (maculo-papular: urticaria pigmentosa) are seen: maculo/papules, nodules/plaques, solitary large cutaneous nodule, diffuse erythrodermic type, and telangiectasia macularis eruptive perstans. Histopathology: Infiltrate composed chiefly of mast cells, which are characterized by the presence of metachromatic granules in their cytoplasm. These granules are visible after staining with Giemsa stain or toluidine blue. By immunohistochemistry mast cells are cKit positive. Further investigations: Blood tryptase, bone narrow biopsy, KIT mutations.

Urticarial rashes, often not itchy can be prodromic or developed during different viral infections. Histology: may be non-specific. If blister formation, degenerative changes in epidermal cells including ballooning and reticular degeneration can be observed. Further investigations: Viral serology.

Occasionally some autoimmune bullous diseases (bullous pemphigoid, dermatitis herpetiformis or Linear IgA bullous dermatosis) are preceded by urticarial reactions. Histopathology: Subepidermal bullae. Direct immunofluorescence; Different patterns of IgG, IgM and IgA binding that help to the histopathologic diagnosis. Further investigations: Indirect immunofluorescence ELISA.

Autoinflammatory syndromes show urticarial rashes and even cold urticaria with systemic involvement, fever and general discomfort. Broad spectrum of familial diseases including e.g Muckle Well syndrome and cryopyrin-associated periodic syndromes (CAPS) and others should be considered.

Neutrophilic dermatosis are included as autoinflammatory conditions often associated with systemic diseases (e.g. Sweet syndrome, acute febrile neutrophilic dermatosis). Histopathology: The histologic finding varies according with the different entities and with different diagnostic relevance. Some show upper epidermal dyskeratosis, increase dermal mucin, and a superficial lymphoid inflammatory infiltrate with occasional neutrophils or eosinophils. Further investigations: C reactive protein, NLRP-3 genotyping in cryopyrin syndrome, high ferritin in adult Still disease, electrophoresis (immunoglobulin and paraproteins) e.g. IgM in Schnitzler Syndrome.

There is no general approach to such diseases with a common treatment.