Dermatology disasters: serious or difficult-to-diagnose skin diseases (Proceedings)

Ischemic dermatoses fall into three categories: dermatomyositis, vaccine- and drug- caused cases, and idiopathic. Dermatomyositis has been reported primarily in collies and Shetland sheepdogs and their crosses, although other breeds have a sporadic incidence of this disease1-3.  As its name implies, the disease affects both the muscles and the skin.  Cutaneous changes include crusts, ulcera­tions, vesicles, and/or alopecia around the muco­cutaneous junc­tions, front legs, ear tips, and tail, though other body areas may be affected.  Claws may be misshapen. Muscular atrophy may be generalized or may be selective, often affecting the temporal and masseter muscles.  Clinical manifes­tations vary, with some dogs showing only skin or muscular signs, while in others both systems are affected.  Serum enzymes such as creatinine phosphokinase (CPK) are usually normal, and muscle involvement often may be proved only by biopsy or electromyography.  Skin biopsies generally reveal perifol­licular mono­nuclear inflammation, and occasionally show intracellular edema of the basal cell layer of the epidermis, with subepidermal clefts; advanced cases show a loss of the normal follicular structures.  Dermal blood vessels may be decreased in number, be over-distended, smudged, hyalinized and/or sclerotic in appearance. The onset of clinical signs usually occurs before the age of 6 months.  The severity of the disease varies greatly, with some dogs improving with age.  Females should be spayed as estrus may exacerbate clinical signs.  Diagnosis is based on clinical signs and skin biopsy. Recently, the disease in Shetland Sheepdogs has been linked to a change in chromosome 354.

Drug- or vaccine induced ischemic dermatosis is most commonly associated with rabies vaccination, manifesting itself as alopecia, scale and crusts, and occasionally ulceration, in the area of the vaccine administration, and rarely, in other places as well (especially the pinnal margins and tail tip. Diagnosis is by clinical signs and biopsy. Histology shows involuting, small hair follicles with prominent connective tissue associated with the  external root sheaths – the follicles will sometimes disappear permanently. Deep dermal vessels will show a plasmacytic/lymphocytic vasculitis; more superficial vessels will appear as noted above for dermatomyositis5.

Idiopathic ischemic dermatosis can occur at any age and any canine breed. Typically, the tail tip, ear margin, face (nasal planum) and sometimes trunk are affected. Claws may be misshapen. Histopathology is as for the vaccine caused type. Recently, there have been anecdotal reports of dogs with this disease having positive Ehrlichia titers and responding completely to doxycyclines – this is probably worth pursuing.

Pentoxifylline (PTX) 10-20 mg/kg q8h, is often effective in controlling ischemic dermatoses. PTX is derived from theobromine.  Pentoxifylline, and other methylxanthines produce anti-inflammatory effects.  PTX also improves blood flow through narrowed arteries because of the rheological property which allows red blood cells to change shape. It is not known if the improvement in patients with ischemic dermatoses are caused by improved blood flow or via the anti-inflammatory mechanisms. Vomiting is occasionally seen as a side-effect.

Erythema multiforme (EM) is an acute eruption of the skin and mucous mem­branes.  It is characterized in human beings clinically by annular ("target") lesions.  While these have been observed in animals, more common signs are mucocutaneous vesicles, ulcers, maculae, and/or urticarial plaques may also be seen.  In widespread lesions, the ventrum and peri-ocular areas are often involved. EM may be self-limiting, although by the time the animals arrive at the specialist's office, this is not often the case.  EM histologically shows apoptotic (programmed-cell death mechanism-activated) keratinocytes, with satellitosis (lymphocytes surrounding the keratinocytes, presumably triggering the programmed cell death mechanism). The incidence/recognition of this disease seems to be increasing. While erythema multiforme has been reported to have an association with drug eruptions, recent work points to TEN (see below) and ‘cross-over syndromes' between the two diseases as more likely to be due to drug involvement6.  Viruses have also been hypothesized to cause EM in small animals, and there is one report of EM caused by parvo virus in a puppy7. The author has seen a few cases that seemed to have an ischemic component, or occurred concurrently with an ischemic dermatitis. While theoretical­ly pentoxifylline should be helpful, the author has seen 2 dogs which had EM induced by pentoxifylline! Intravenous human immunoglobulin has been reported as successful in two dogs when infused on 2 consecutive days (1 g/kg per day)8. This is a relatively expensive treatment.

Rare Neutrophilic & Eosinophilic Disaster Syndromes

These include 4 rare conditions which are often typified by neutrophils in the skin, and 1 by eosinophils in the skin, but with different underlying causes, and therefore treatments.

Necrotizing fasciitis (‘flesh-eating' bacteria) caused by Streptococcus canis (biotype 3). Dogs present with fever, swelling, erythema, disproportionate pain on palpation, draining tracts and ulcers. There is rapid progression of this disease, as there is of all three diseases in this group. Diagnosis is by clinical signs, skin biopsy and bacterial culture and susceptibility; treatment is surgical debridement when necessary, and antibiotics – eventually based on susceptibility results, but initially with either clindamycin or amoxicillin-clavulanate.9 Do not use fluoroquinolones, as these have been associated with possibly engendering or enhancing the extreme toxicity of these Streptococcus strains.

Sweet's (sterile neutrophilic dermatosis) syndrome is a non-infectious, presumed immune mediated condition typified by erythema, fever, malaise, neutrophilia, lameness and nuetrophilic effusions into the joints. This is also a rapidly progressive disease, and may be caused by certain medications10a, as well as arising spontaneously. There is one report of a dog with internal organ involvement. Diagnosis is based on skin biopsy, the lack of bacteria on culture of intact skin lesions or joint aspirates, and response to corticosteroids (prednisolone 1 mg/kg bid initially).

Sterile Pustular Erythroderma of Miniature Schanuzers

A rare, severe, often fatal disease, seemingly limited to miniature Schnauzers, often preceded by bathing. This condition presents with severe depression and malaise, often with fever. Skin lesions are (often dramatic) erythema, pustules or epidermal collarettes, and/or wheals. These dogs are very sick – treatment, when successful, consists of high dose corticosteroids.11In a recent abstract, a contact reaction to one of the components in an aloe-based shampoo was implicated.

Staphylococcal Toxic Shock is caused by Staphylococcus sp, presumably Spseud- intermedius. Erythema, fever, malaise, and neutrophilia are seen initially; the malaise may be severe and edema of the legs may develop as the disease progresses. This may be the most rapidly progressing of these three diseases. Diagnosis is based on clinical signs – a skin biopsy and bacterial susceptibility should be performed, but any suspicion on the veterinarian's part for this disease should initiate the immediate use of staphylocidal antibiotics – cephalosporins have been recommended. Pugs may be over-represented.

Well's like syndrome is a eosinophilic, generalized dermatitis to cellulitis. It has been associated with either GI signs and/or drugs in some, but not all cases. Peripheral eosinophilia is rare. Skin lesions are papules, macules, and erythema. Pruritus is variable. Histopathology shows an eosinophilic dermatitis, often with eosinophilic ‘flame figures' (collagen surrounded by eosinophils or their granules). Treatment consists of prednisolone/prednisone at 1-2 mg/kg, then tapered. Treatment duration is variable, but should be continued for at least one month.

References

Hargis AM, Mundell A. Famillial canine dermatomyositis. Comp Cont Ed Pract Vet 1992; 14:855-65.

Hargis AM. A skin disorder in three Shetland sheepdogs: comparison with familial canine dermatomyositis of Collies. Compend Cont Ed Pract Vet 1985; 7:306-15.

White SD, Shelton D, Sisson A, et al. Dermatomyositis in an adult Pembroke Welsh  corgi.  J Am Anim Hosp Assoc 1992; 28:398-401.

Clark LA, Credille KM, Murphy KE, et al. Linkage of dermatomyositis in the Shetland Sheepdog to chromosome 35. Vet Dermatol 2005;16:392-394.

Vitale CB, Gross TL, Magro CM. Vaccine-induced ischemic dermatopathy in the dog. Vet Dermatol 1999; 10:131-142.

Hinn AC, et al. Erythema multiforme, Steven-Johnson syndrome, and toxic epidermal necrolysis in the dog: clinical classification, drug exposure, and histopathological corelations. J Vet Allergy and Clinical Immunology 1998 6:13-20.

Favrot C, Olivry T, Dunston SM, et al. Parvovirus infection of keratinocytes as a cause of canine erythema multiforme. Vet Pathol 2000 37: 647-9.

Trotman TK, Phillips H, Fordyce H, et al. Treatment of severe adverse cutaneous drug reactions with human intravenous immunoglobulin in two dogs. J Am Anim Hosp Assoc 2006; 42:312-320.

Naidoo SL, Campbell DL, Miller LM, et al. Necrotizing fasciitis: a review. J Am Anim Hosp Assoc 2005 ;41:104-9.

Ingrey KT, Ren J, Prescott JF. A fluoroquinolone induces a novel mitogen-encoding bacteriophage in Streptococcus canis. Infect Immun 2003 ;71:3028-3033.

Mellor PJ, Roulois AJ, Day MJ et al. Neutrophilic dermatitis and immune-mediated haematological disorders in a dog: suspected adverse reaction to carprofen. Journal of Small Animal Practice 2005; 46: 237–42.

Johnson CS, May ER, Myers RK, et al. Extracutaneous neutrophilic inflammation in a dog with lesions resembling Sweet's Syndrome. Vet Dermatol 2009; 20:200-5.

Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Blackwell Publishing, Oxford, UK. 2005; 20-22, 84-86, 366-388.

Murayama N, et al. A case report of superficial suppurative necrolytic dermatitis of miniature Schnauzers with an identified causative agent using patch testing. Proceedings of the North American Veterinary Dermatology Forum, 2008, pg 197.

Morris DO, Gomez SM, et al. Eosinophilic dermatitis with edema in nine dogs, compared with eosinophilic cellulitis in humans. J Am Vet Med Assoc 1999; 215:649-653.

Palmeiro BS, Goldschmidt MH, et al. Comparison of clinical history and dermatologic findings in 29 dogs with severe eosinophilic dermatitis: a retrospective analysis. Vet Dermatol 2006; 17:338-347.