Peter J. Ihrke, VMD, DACVD
Department of Medicine & Epidemiology, School of Veterinary Medicine, University of California, Davis
Davis, CA, USA
Secondary organism overgrowth and skin infections with pathogens such as Staphylococcus intermedius and Malassezia pachydermatis are ubiquitous in dogs. Pruritic secondary infections are especially common in dogs with allergic skin disease and may act as important flare factors for allergic skin diseases. Thus secondary organism overgrowth or infection are common causes of increased pruritus in already itchy dogs. Surface cytology is the only good way to determine organism overgrowth. Consequently, cytologic examination of smears from inflamed skin should be performed at every allergy re-evaluation and when the patient is experiencing a flare of pruritus. Stained slides are evaluated on a microscope using both high dry power and then an oil emersion lens for bacteria (especially cocci), Malassezia yeast, and inflammatory cells.
Possible underlying causes of recurrent canine pyoderma can be categorized as persistent underlying skin disease, bacterial hypersensitivity, immunodeficiency, resistant strains of Staphylococcus spp., and non-Staphylococcal pyoderma. Persistent underlying skin disease are by far the most common cause of recurrent pyoderma. The most commonly documented persistent underlying skin diseases include non-parasitic allergic diseases (atopic dermatitis, food allergy), parasitic allergic diseases (flea allergy, scabies, cheyletiellosis), demodicosis, endocrine diseases, diseases of cornification, genodermatoses, occult neoplasia, and immunodeficiency (congenital, acquired).
Pruritus in recurrent pyoderma is a key feature in the prioritization and differentiation of underlying causes. If pruritus disappears after antibiotic therapy, this is indicative that the pyoderma caused the pruritus. If pruritus remains, one must look for underlying pruritic skin disease. Common pruritic, persistent underlying skin diseases include non-parasitic allergic skin diseases (atopic dermatitis, food allergy), allergic parasitic skin diseases (flea allergy dermatitis, sarcoptic acariasis), primary cornification defects, and coexistent secondary Malassezia dermatitis.
The goals of long-term management of recurrent pyoderma include the prevention of recurrent episodes of pyoderma, or diminishing the frequency of recurrence. This requires long-term management of underlying skin diseases or other predisposing causes. Most dermatologists affirm that canine atopic dermatitis is the most commonly diagnosed underlying cause of recurrent pyoderma. Rigorous investigation for underlying skin diseases or other predisposing causes should be initiated if a dog does not respond completely to appropriate therapy. Dogs with either recurrent infections or infections that do not respond completely to appropriate therapy should have antibacterial shampoos twice weekly. Immunomodulatory therapy may be helpful adjunctively. The use of extended regimens of antibiotic therapy should be considered if other therapy has not prevented recurrence.
The rationale for antibacterial shampoo therapy includes decreasing surface bacteria, and limiting recolonization. Active agents include benzoyl peroxide, benzoyl peroxide and sulfur, chlorhexidine, triclosan and ethyl lactate. Unfortunately, the ideal frequency probably is 2 or 3 times weekly allowing 15 minutes of contact time. Unfortunately repetitive antibacterial shampoo therapy interferes with modern spot-on flea control.
The rationale for immunomodulatory therapy includes the stimulation of enhanced immune surveillance, and altered response to bacterial allergen leading to diminished recurrence. The only killed bacterial product supported by double-blind placebo-controlled data is Staphage Lysate®--SPL--(Delmont Labs). This product is made from S. aureus of human origin. Either .5 c.c. is injected twice weekly or 1 c.c. is injected weekly subcutaneously.
Extended regimens of antibiotics should be considered if underlying causes either are not identified or cannot be managed, antibacterial shampoo therapy is not successful, immunomodulatory therapy is either not successful or has been rejected. Extended antibiotic regimens should be considered as a last resort. The rationale behind extended antibiotic regimens includes diminished recurrence by preventing re-infection. Favored dosing options include two or three consecutive days per week dosing at the full daily dose or every-other-week dosing with an attempt at extending the "off" period to 2 and then 3 weeks. Antibiotic choices include cephalexin, cefpodoxime, fluoroquinolones (enrofloxacin, marbofloxacin), and clavulanate-potentiated amoxicillin.
Long-term owner compliance is required for extended antibiotic regimens to be successful. Compliance, the study of recommended therapy versus delivered therapy, is poorly studied in veterinary medicine. Studies in human medicine indicate that up to 40% of prescriptions are never filled and of those filled, up to 40% are taken incorrectly. Drugs requiring once a day dosage may lead to better owner compliance.
Treatment failure with extended regimen antibiotic therapy may be caused by lack of recognition or successful management of underlying disease (especially pruritic disease and especially allergy), inadequate duration of curative antibiotic therapy prior to switching to extended regimens, inadequate owner compliance, or resistance to the antibiotic.
Canine Malassezia Dermatitis
Malassezia dermatitis is a common canine skin disease caused by Malassezia pachydermatis (Pityrosporum pachydermatis, P. Canis). It has long been known as a ubiquitous commensal organism in the dog that resides on or in the skin, ear canals, anal sacks, vagina and rectum. It has now been recognized as a ubiquitous secondary pathogen responsible for pruritus. In 1987, Malassezia pachydermatis was controversially implicated by Mason as a cause of pruritic, inflammatory skin disease in dogs. Mason hypothesized that alterations in host defense mechanisms and skin surface microclimate allow the organism to become a facultative pathogen.
The role of hypersensitivity and Malassezia dermatitis remains controversial. Atopic dogs with Malassezia dermatitis developed an IgE-mediated, type 1 hypersensitivity to intracellular protein extracts of M. pachydermatis. In addition, both immediate and delayed hypersensitivity reactions have been seen in dogs with seborrheic dermatitis. As Malassezia dermatitis may well be a disease of hypersensitivity, the number of organisms required to cause clinical disease is not defined. Surface yeast colonization without tissue invasion can lead to disease. Concurrent colonization or infection with Staphylococcus intermedius may enhance the inflammation seen with Malassezia dermatitis.
As veterinarians, it behooves us to be aware that the organism found in dogs may act as an opportunistic nosocomial pathogen in humans. An outbreak in low-birth-weight neonates in an intensive care nursery showed Malassezia dermatitis in a health care workers dog to be the cause of the outbreak.
Predisposing causes for the Malassezia dermatitis include allergic skin disease (especially atopic dermatitis), diseases of cornification, chronic or recurrent inflammatory skin disease and previous treatment with antibiotics or corticosteroids. Reported breed predilections include the Basset Hound, Springer Spaniel, German Shepherd Dog, West Highland White Terrier, Silky, Maltese, Chihuahua, Poodle, Shetland Sheepdog, Dachshund and the Australian Terrier. The Newfoundland may also be at increased risk.
Mason initially reported three distinct syndromes including primary and secondary Malassezia dermatitis plus a very rare syndrome characterized by severe pruritus and self-trauma. Secondary Malassezia dermatitis is seen most commonly and is linked to chronic, inflammatory skin disease. It is characterized by a strong "seborrheic" odor and severe pruritus. Primary Malassezia dermatitis offers identical symptomatology but responds rapidly and completely to anti-yeast therapy without recurrence. The third very rare presentation is severe pruritus and self-trauma localized to the muzzle or perianal area, and may be perceived by owners to be seizure activity.
Lesions may be focal, multifocal or generalized. Erythema, hyperpigmentation, alopecia, lichenification, scaliness and/or greasiness, exudative dermatitis and a "musty" seborrheic odor are noted. Pruritus is the common unifying clinical feature. Lesions may be sharply demarcated and closely adjacent skin may be un-inflamed and normally haired. Alopecic, greasy, lichenified lesions gradually expand peripherally. Site predilections include the ventral neck, ventral abdomen, axilla, face, pinna, feet, forelegs and any skin folds.
Skin cytology is the diagnostic procedure of choice. Skin biopsy is less useful. Yeast culture is not recommended. Skin biopsy may not be helpful as the histopathology of lesions with large numbers of organisms identified by cytology may not exhibit organisms. This seeming discrepancy could be explained by a non-linear distribution of organisms or removal of organisms during automatic processing.
Controversy exists as to the best method of harvesting organisms. Skin scraping, cotton swabs, direct impression smears, tape stripping and "sticky" glass slides have been recommended. In dry skin scraping, the material obtained is smeared onto a glass slide. If dry cotton swabs are used, the harvested debris is transferred to glass slides. Direct impression smears may be performed where a glass slide can be firmly pressed against the affected area. Clear cellophane tape stripping may be used to acquire debris with the tape used as a cover slip applied to a ribbon of stain on a glass slide. Specimens are stained with a rapid stain (Dif Quik®) and examined under oil emersion. The presence of at least three or four organisms per oil emersion field is considered significant by many dermatologists.
To establish a diagnosis, the clinician must have suggestive clinical lesions and find the organisms in sufficient number to be considered a pathogen. Identification of predisposing underlying causes is the key to management success. If Malassezia dermatitis is treated simply as the pathogenic proliferation of yeast, than reoccurrence after therapy is the rule.
Rational therapy requires the ongoing management of documented underlying disease(s) or predisposing causes. The clinician must control or cure underlying causes, kill the yeast, combine systemic and topical therapy and hope that the disease does not recur!
Systemic antifungal therapy is most likely to induce speedy resolution of lesions and diminish the number of organisms. The availability of generic ketoconazole has greatly diminished the cost of therapy (200 mg. tablets ~ $ 0.80 or less each) However, systemic therapy is still expensive, especially in larger dogs. Ketoconazole is given orally at a dosage of 5mg/kg once daily for a minimum of thirty days. (Some improvement seen may be due to the potent anti-inflammatory effects or effect on keratinization seen with ketoconazole). Some dermatologists advocate monitoring liver enzymes during therapy due to the controversy of possible hepatotoxicity in humans. Alternatively, itraconazole (Sporonox®--Janssen) can be given 5mg/kg (PO, once daily) or fluconazole (Diflucan®--Roerig) orally, 5 mg/kg once daily. Fluconazole is now available as a generic drug.
Topical shampoo therapy is an essential adjunct therapy. It can be used as sole therapy if financial constraints are present. A minimum of twice weekly for at least six weeks is required. Useful products include miconazole/chlorhexidine gluconate--MalaSeb® (Dermacare, IVX), ketoconazole/chlorhexidine gluconate--KetoChlorTM, and acetic acid/boric acid--MalaAcetic® (DermaPet). The performance of topical leave-on rinses has been disappointing. Enilconazole (Imaverol®--Janssen) is available in some countries.
Recurrent Malassezia dermatitis is common problem and is one of the most frustrating canine skin diseases. Similar to recurrent pyoderma, persistent underlying skin disease are the most commonly diagnosed cause of recurrent Malassezia dermatitis. Recurrent Malassezia dermatitis and recurrent superficial pyoderma frequently occur together. At-risk dogs should be shampooed at least 2 times per week. Antifungal shampoo should be used adjunctively in all cases of recurrent Malassezia dermatitis. Extended regimens of ketoconazole may be useful.
1. Scott DW, Miller WH, Griffin CE: Muller and Kirk's Small Animal Dermatology. 6th edition, W. B. Saunders Company, Philadelphia, 2001, pp 274-288.
2. Ihrke, PJ: Bacterial Skin Disease in the Dog: A Guide to Canine Pyoderma. Veterinary Learning Systems, 1996, pp 63-88.
3. Ihrke PJ: Bacterial Infections of the Skin. In Green CE (ed): Infectious Diseases of the Dog and Cat, Third Edition, Philadelphia, WB Saunders Co, 2006, 807-815.
4. Carlotti DN, Jasmin P, Gardey L, Sanquer A. Evaluation of cephalexin intermittent therapy (weekend therapy) in the control of recurrent idiopathic pyoderma in dogs: a randomized double-blinded, placebo-controlled study. Vet Dermatol 2004;15s: 8-9.
5. Mason KV, Evans AG: Dermatitis associated with Malassezia pachydermatis in 11 dogs. J Amer Anim Hosp Assoc 27:13-20, 1991.
6. Chang HJ, Miller HL, Watkins N et al: An epidemic of Malassezia pachydermatis in an intensive care nursery associated with colonization of health care worker's pet dogs. New England Journal of Medicine 338:706-711, 1998.
7. Bond R, Patterson-Kane JC, Lloyd DH: Clinical, histopathological and immunological effects of exposure of canine skin to Malassezia pachydermatis. Med Mycol. 42(2), 165-75, 2004.