Introduction

The skin is a target for many microbial infections. The most common are associated with overgrowth of commensal organisms such as Staphylococcus intermedius and Malassezia spp. or invasion by transient pathogens such as Pseudomonas spp. However, less commonly the skin may give clues about the presence of systemic infections. Besides providing visible diagnostic clues to systemic infectious diseases, the skin is also readily accessible for non-invasive tests such as cytological techniques and biopsy for culture, histopathology, special stains, immunostaining and molecular diagnostics.

Systemic Infections That Enter By the Cutaneous Route

Feline Mycobacterial Infections

Exposure to Mycobacterium tuberculosis and M. bovis can cause classical tuberculosis (TB) in cats. The increase in badger TB cases appears to have been paralleled by an increase in the number of M. bovis cases in cats, although the epidemiology has not been investigated in detail. Cats may develop cutaneous TB secondary to infected bites or scratches. Another organism M. microti (wildlife reservoir), is more commonly isolated than either M. bovis or M. tuberculosis and may also cause systemic spread.

The primary inoculation site appears to be the skin and the presence of cutaneous lesions in combination with submandibular/prescapular lymphadenopathy should alert the clinician to presence of this group of infections. Nodules, draining sinus tracts and ulceration may be seen affecting the face, extremities, tail base and perineum: all sites compatible with bite injuries. Extension of the granulomatous lesions to subcutaneous tissue, muscle, joints and bone and pulmonary involvement may be present. M. bovis infection is notifiable in the UK irrespective of species and appropriate clinical signs and/or histopathological findings (especially positive Ziehl-Neelsen (ZN) staining) require further confirmation by bacteriological culture and species characterisation.

The two other mycobacterial syndromes seen in the cat, feline leprosy and infection with opportunist mycobacteria (e.g., M. smegmatis, M. fortuitum/chelonae) primary affect the skin and cause panniculus. They rarely cause extension to bone or systemic disease.

Actinomyces/Nocardia Infection

The primary route of Actinomyces infection is via skin penetration and infection may spread systemically to produce osteomyelitis and infection of body cavities, i.e., peritonitis. Cutaneous signs are characterised by cellulitis, multiple draining sinus tracts and abscesses. 'Sulphur granules' may be seen in the exudate. The organism can be identified using cytology from the exudate of a draining sinus tract, or, more usefully, from an impression smear of sulphur granules. Nocardia infection has a similar pathogenesis and may produce disseminated, abdominal or pleural disease as well as cutaneous signs. Confirmation of these diseases requires culture.

Borreliosis

In Europe, infection with Borrelia afzelli is a cause of erythema chronicum migrans in humans. Anecdotal evidence suggests that this lesion also occurs as a marker for Lyme disease. Diagnosis is particularly difficult as many dogs (and cats) in the UK appear to be exposed to non-pathogenic genotypes. Consequently serology is difficult to associate with clinical signs. In humans culture and polymerase chain reaction (PCR) using skin biopsies from classical lesions is used to confirm diagnosis.

Leishmaniasis

Leishmania infantum infection in dogs (and cats) produces a combined syndrome of cutaneous and polysystemic disease. Exfoliative dermatitis and alopecia particularly of the periocular regions, pinnae, nasal planum, pressure points and extremities is common. Ulceration and nodule formation may occur as well. Non-systemic signs of weight loss, muscle atrophy, partial anorexia, lymphadenopathy and fever are associated with signs referable to polyarthritis, glomerulopathy, panophthalmitis and haemolytic anaemia. Multiple autoantibodies are produced and animals may show Coombs' and autonuclear antibody positivity and hypergammaglobulinaemia. Diagnosis involves a combination of serology, PCR and identification of amastigotes in cytological /biopsy specimens.

Subcutaneous/Deep Systemic Fungal Infections

Cryptococcosis is caused by a saprophytic yeast-like fungus, which develops a large capsule in affected tissue. It is considered to have a ubiquitous, world-wide distribution. Cryptococcus neoformans (var. neoformans, var. gattiei) produces clinical signs primarily referable to the skin and respiratory tract in affected cats and dogs and these may be markers for involvement of the central nervous system and eye. Multiple cutaneous nodules commonly involve the head, bridge of nose and periocular regions. Upper respiratory tract signs referable to nasal granuloma are common. Uveitis, optic neuritis, retinal detachment and neurological signs referable to the site of granuloma formation have been reported. Diagnosis is by demonstration of the encapsulated organism in cytology specimens or in periodic acid-Schiff (PAS)-stained biopsy specimens. The organism may be cultured from both exudate and tissue samples. Serological detection of capsular antigen has been used in the diagnosis of cryptococcosis.

Systemic Infections That Induce Cutaneous Bleeding

Vasculopathies

Skin diseases with underlying dermal vasculitis are uncommonly recognised in the dog and cat. This may be due to the fact that the signs of the underlying disease may dominate the clinical appearance. The skin lesions may be small, circumscribed, covered with crusted material and distributed in areas of the body that may not be routinely checked, i.e., foot pads, tail tip, scrotum and pinnae. The pathogenesis involves type III hypersensitivity whereby circulating immune complexes are lodged within the small vessels of these areas of skin, initiating vasculitis and thrombosis with ischaemic necrosis of the skin supplied by the vessel. The causative antigens are rarely identified but vasculitis may occur as part of underlying infectious systemic disease and in response to vaccine antigens (e.g., rabies vaccine). There are many examples of systemic infections causing vascular disease. Ehrlichiosis and infections with Rickettsia spp. are associated with vasculitis and signs of intracutaneous bleeding. In some cases of Rickettsia rickettsii infection, ear tip and footpad necrosis has been reported. In cats, thromboembolic disease associated with cold reacting agglutinins associated with haemoplasma infection has been reported.

Areas with minimal collateral circulation such as the pinnae, feet (both clawbeds and footpads) and tail tip are often predisposed sites although lesions may occur anywhere in the skin. Affected animals present with multiple foci of cutaneous ulceration and crusting. Early lesions (rarely seen) include petechiation, haemorrhagic bullae and maculae. Later lesions relate to skin necrosis. Thrombosis of deep vessels may result in sloughing of deep tissue several days to weeks after the hypoxic insult. Both general and specific signs related to the underlying disease are common but may be limited to fever of unknown origin. Multiple skin biopsies of fresh lesions may be required to identify the characteristic histopathological features. Immunohistochemistry may demonstrate deposition of immunoglobulin and/or complement within vessel walls, but is generally only of use when lesions are less than 18 hours old. Adjunct immunodiagnostic testing may reveal increased levels of circulating immune complexes, decreased serum complement and hypergammaglobulinaemia.

Coagulopathies/Platelet Disorders

The skin has a large network of dermal blood vessels and the presence of intradermal haemorrhage (petechiation or ecchymosis) is a major clinical sign of systemic infections associated with immune-mediated thrombocytopenia (e.g., ehrlichiosis), consumptive coagulopathies (many infectious diseases causing septicaemia) and complex combinations of both (e.g., angiostrongylosis).

Infection-Induced Pemphigus Reactions

Microbial organisms and/or their products localised in the epidermis or epidermal structures may act as triggers for inducing an immune-mediated reaction against epidermal components. The clinical presentation may start as a cutaneous reaction and distribution characteristic for that infection (e.g., Staphylococcus or dermatophytes) but change, despite appropriate therapy, to a more severe crusting disease affecting face, feet and trunk.

Toxic Epidermal Necrolysis and Erythema Multiforme

These serious syndromes may have an immune-mediated pathomechanism and are markers for serious infectious diseases, drug reactions or malignant neoplasia. However, many are idiopathic. Erythema multiforme (EM) is characterised by spreading erythematous arciform, annular or 'target' lesions with necrosis and ulceration. There is a very suggestive histopathological picture and skin biopsy often provides the clue. Toxic epidermal necrolysis (TEN) is much more serious and both syndromes may be part of the same spectrum. Full-thickness necrosis and ulceration of the skin and mucous membranes occur even from gentle mechanical friction. It is a potentially life-threatening syndrome depending on the area of skin affected. Animals may be febrile, depressed and painful. Any part of the skin or mucous membrane surfaces may be affected. Like EM, the diagnosis is confirmed on biopsy. Full investigation of under lying infections is warranted.

Drugs and Bugs

In many cases where infection is suspected as the underlying cause of systemic disease, appropriate antibiotic therapy will have been administered. Several of the cutaneous syndromes mentioned above could be triggered by drugs and a detailed history that indicates deterioration after the drugs were first administered is required. If in doubt, change the group of antibiotics being used to one that is not related.