Case 3 170707 (16N3574)
Conference Coordinator: Wesley Siniard
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Two-year-old, male castrated dachshund
This dog was presented for evaluation of diffuse erythema, urticaria, and a recently diagnosed femoral artery thrombus. On initial physical exam, the patient was tachypneic with an increased respiratory effort, and with the diffuse skin lesions noted by the original clinician. Some skln lesions progressed to ulcerative lesions, and an absent left femoral pulse. A complete blood count indicated severe neutropenia with a left shift and marked toxicity. An abdominal ultrasound confirmed a distal, femoral artery thrombus. Thoracic radiographs indicated diffuse interstitial to alveolar, patchy to nodular infiltrates compatible with thromboembolic disease. Throughout the afternoon, the dog’s mentation progressively declined. He became hypotensive and acidemic. Due to poor prognosis and concern for sepsis the owner elected euthanasia.
Coalescing epidermal ulcerations were present on all four extremities ranging from 0.5 x 0.5 cm to 2.5 x 3 cm. Ulcers were most severe on the caudomedial aspect of the left thoracic limb. Multifocal to coalescing bullae with central raised areas of pale tan skin were located along the ventrum. When gently traumatized, bullae remain intact. Most bullae were surrounded by a red rim and were most abundant in the inguinal and medial pelvic limb regions. Multifocal to coalesing red foci and three, approximately 1.2 x 0.8 cm ulcers were scattered along the ventrum.. The interdigital spaces were all diffusely red.
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The slide has two sections of haired skin, both of which are variably affected by the same process involving necrosis and inflammation centered on the epithelium. In one section, there is a relatively abrupt transition from essentially normal epidermis to a central, segmental region of full-thickness epithelial necrosis overlying a broad subepidermal cleft. The affected epidermis is infiltrated by large numbers of neutrophils, and is diffusely hypereosinophilic. The process extends into the infundibula of hair follicles. Affected regions have numerous keratinocytes with brightly red dense cytoplasm and shrunken, hyperchromatic nuclei (interpreted as apoptosis), which become more infrequent at the margins of affected areas. The affected area has a dense infiltrate of mixed inflammatory cells in the superficial dermis and in perifollicular areas, consisting mostly of macrophages and neutrophils. Many neutrophils exhibit degenerative changes, characterized by highly segmented and occasionally fragmented nuclei. There are prominent thrombi in superficial subcutaneous veins. The second section is similarly but more severely affected, with broad central ulceration and large numbers of presumed apoptotic keratinocytes leading to coalescing necrosis. Apoptotic cells are more individualized towards the margins. Numerous neutrophils are associated with the epidermal changes. The dermis has a similar inflammatory infiltrate superficially and surrounding hair follicles and adnexae.No special stains.
Skin: Severe, acute, perivascular to diffuse, neutrophilic dermatitis with marked neutrophilic exocytosis associated with epidermal and follicular wall apoptosis and necrosis, and subepidermal clefting Skin: Marked, multifocal, acute thrombosis and hemorrhage
The presence of keratinocyte apoptosis with neutrophilic satellitosis and marked neutrophilic dermatitis with numerous degenerative neutrophils is consistent with staphyloccal toxic shock syndrome (TSS). Morphology of the samples from necropsy were compared to biopsy samples; the latter showed much milder features. The fast decline of the patient as well as additional findings upon necropsy ( widespread neutrophilic thrombosis and necrosis in multiple organs) support the diagnosis of TSS. In toxic shock syndrome, Staphylococcal toxins stimulate massive release of tumor necrosis factor alpha (TNF-alpha), which leads to epidermal devitalization and along with interleukin-1 leads to shock (Gross et al., 2005). In the discussion it is stressed that even with mild features of TSS, it is crucial to act immediately with administration of Beta-lactam antibiotics to avoid rapid decline and death of affected patients.
Conference attendees mentioned differential diagnoses of erythema multiforme and toxic epidermal necrolysis. However, both these diseases are associated with lymphocytic satellitosis, accompanying the keratinocyte apoptosis. With the latter there are massive coalescing foci apoptosis. Neither erythema multiforma nor toxic epidermal necrolysis are associated with a remarkable neutrophilic dermal or epidermal infiltrate.