Microbial overgrowth may be defined as a clinical disease due to the colonisation of the skin by microbes. In the dog, this includes Malassezia overgrowth (MOG) due to Malassezia pachydermatis and bacterial overgrowth (BOG) due to Staphylococcus intermedius.
Malassezia Dermatitis (or MOG) in the Dog
The lipophilic but not lipodependent yeast Malassezia pachydermatis is a component of the normal cutaneous flora of the dog. Around 50 % of healthy dogs are carriers (external ear canal, skin--anal area, lips and extremities--, haircoat). The response of the host to the yeast includes non-specific defense mechanisms (phagocytosis by neutrophils) as well as cell-mediated specific defense mechanisms. Local delayed hypersensitivity responses and/or innate immune mechanisms (transferrin limiting microbial access to iron) play an important role.
Aetiology and Pathogenesis
Alterations of the cutaneous microclimate or host defense mechanisms allow Malassezia pachydermatis to multiply and to become pathogenic. These changes may be due to underlying causes (ectoparasitic, allergic, endocrine and keratinization disorders, treatment with glucocorticoids or antibiotics). It has also been suggested that innate immunity is abnormal in case of MOG. Particularly, a defect in the production of antimicrobial peptides (AMP) and Toll-like receptors may be implicated since they may be important in innate skin immunity against fungi. Also, specific immunological dysfunction (cell-mediated immunity, IgA secretion) could promote the growth of the Malassezia population on the skin and its pathogenicity.
Malassezia produce many enzymes (including lipases and proteases) which can contribute to cutaneous inflammation through proteolysis, lipolysis (which alters the lipid cutaneous film), changes of cutaneous pH, eicosanoid release and complement activation. In addition, it has been shown that Malassezia pachydermatis could play an allergenic role in regard to a type 1 (immediate) hypersensitivity. Skin-testing with a Malassezia extract may show immediate hypersensitivity reactions. Recently, the functionality of anti-Malassezia IgE has been demonstrated through passive transfer using the Prausnitz-Küstner technique. Some major allergens of Malassezia pachydermatis have been identified: proteins with 45, 52, 56 and 63 kDa molecular weight. The delayed hypersensitivity response is less well known. Patch-testing (epicutaneous tests) has been evaluated recently and may be a good tool to explore delayed hypersensitivity caused by the yeast.
There is no age or sex predilection. Some breeds are predisposed to Malassezia dermatitis (e.g., West Highland white terrier and Basset hound). Malassezia dermatitis is often seasonal (summer). There is no indication that Malassezia dermatitis is contagious.
Pruritus is always present and severe. Animals are presented with a strong odour of rancid fat.
At the beginning of the disease there is localized or diffuse erythema, erythematous papules and macules, and a keratoseborrhoeic disorder with scaling, crusting, alopecia and a greasy aspect of the skin and hair. This is followed rapidly by secondary lesions such as lichenification and hyperpigmentation. Malassezia dermatitis may be localized, e.g., on the ventral side of the body (neck, axillae, ventrum and inguinal area), face (ear pinnae, lips, muzzle), peri-anal area and legs (forearms, caudal thighs and feet). It may also be generalized. Concurrent otitis externa is common.
Diagnosis of Malassezia dermatitis is based upon history, physical examination, appropriate complementary diagnostic aids to show the presence of Malassezia on the skin, response to specific therapy and exclusion of other dermatoses.
Cytological examination may show yeasts and allow for a semi-quantification. The result is immediate using the immersion power objective after staining with a rapid method. Several cytological techniques can be used: impression smear, « scotch test » using pieces of tape (clear cellophane) strip, scrape smear, swab smear. Impression and above all tape strip smears appeared to be the most reliable methods. Swab smears should be reserved for the external ear canal. Cytological examination will show oval or elongated cells of 3 to 5µm in diameter, with a typical single polar budding. The minimal number of yeasts which indicates the possibility of a true Malassezia dermatitis is not precisely known. In addition there are variations between breeds and body sites. Lastly there are cases in which a small number of yeasts trigger a hypersensitivity reaction.
Fungal cultures may show the presence of Malassezia on the skin and hair of dogs (Sabouraud's dextrose agar with chloramphenicol and cycloheximidine and modified Dixon's agar which grow all species). As the yeast is a normal component of the cutaneous flora of the dog, by itself a positive culture has little or no value.
Cutaneous histopathology may sometimes show the yeasts on the surface of the epidermis and in the infundibula, particularly in PAS stained sections (although they are occasionally visible on HE stained sections). However if they are not discovered this does not exclude their presence (biopsy in a non-infected area, removal of the stratum corneum during processing, etc). Cutaneous histopathology is a less sensitive technique than cytology. There are common findings in biopsies from dogs with Malassezia dermatitis, including supepidermal linear alignment of mast cells (SLAM). Signs of concurrent bacterial folliculitis or BOG are not uncommon.
The therapeutic challenge is in fact the ultimate tool to confirm that in a particular case the commensal Malassezia has become a pathogen.
Differential diagnoses include many pruritic dermatoses with erythema, hyperpigmentation and seborrhoea including parasitic and allergic skin diseases, bacterial folliculitis and all causes of seborrhoea with cutaneous inflammation.
Systemic therapy is necessary in many cases, particularly when clinical signs are severe and when the lesions are extensive. Ketoconazole is the most commonly used drug. The dose is 10 mg kg-1/day (up to 200 mg/day). It is recommended to give the drug with some food. Tolerance is usually good but periodic biochemistry panels are necessary if the drug is given over an extended period of time. Itraconazole may also be used (5 to 20 mg kg-1 every day or other day).
Topical therapy is an alternative to systemic treatment, particularly for localized lesions (creams, gels, lotions or sprays). A soothing astringent topical spray (Dermacool®, Virbac), has been proved effective in Malassezia pododermatitis (Carlotti and Rème, 2004). For extensive lesions antifungal shampoos or lotions are preferable. They can be used with systemic therapy, which speeds up recovery. This form of topical therapy should not be used alone as a diagnostic challenge, but it can maintain a remission, thus confirming the diagnosis. Shampoos containing miconazole (2%), chlorhexidine (at least 3%), a combination of both (2% each) and ketoconazole (2%) are the best whereas the most appropriate leave-on rinses (lotions) are lime sulfur and above all enilconazole (10% diluted 50 times i.e., 0.2%). Topical treatments should be administered 2 to 3 times a week for 2 weeks then once a week.
Therapeutic follow-up is very important. Pruritus usually decreases within one week, whereas lesions will clearly decrease after 2 weeks. The duration of treatment should be at least one month. Usually therapy is continued for 7 to 10 days beyond clinical cure. Otitis externa should be treated vigourously to limit the fungal reservoir. It is important to diagnose and treat appropriately an underlying cause.
Bacterial overgrowth has been recently recognized (Pin D, Carlotti DN et al, 2006), although indications in the veterinary literature have suggested its existence for more than 10 years.
Aetiology and Pathogenesis
The disease is due to a staphylococcal (Staphylococcus intermedius) overgrowth at the surface of the skin of affected dogs. The pathogenesis of the disease is in fact unknown. Low levels of anti-staphylococcal IgE exclude a hypersensitivity process but high levels of IgG suggest that the affected animals have experienced a staphylococcal infection. Bacterial toxins can have an allergic role and can act as superantigens triggering non-specific inflammatory reactions. An important phenomenon to be considered in BOG is quorum sensing: when a certain density level of staphylococci is exceeded, they express particular characteristics and switch their metabolism from cell proliferation to toxin production.
It is likely that a number of cases are secondary to an underlying allergic skin disease and perhaps also to glucocorticoid therapy, which could be a perpetuating cause. In fact, it has been demonstrated that bacterial adhesion is higher in atopic dogs than in normal dogs (Simou, Thoday et al, 2005). In addition, atopics are lacking antimicrobial peptides (cathelicidins, beta-defensins) and this contributes to microbial colonization. There is evidence from an experimental model of canine cutaneous type I hypersensitivity that injection of a mast cell degranulator or histamine intradermally renders the overlying epidermis more permeable to bacterial antigens (Mason and Lloyd, 1990). Last but not least microbial colonization triggers an auto-sensitization by molecular mimicry, which may be a component of the pathogenesis of atopic dermatitis in humans.
No data is available but it is likely that breed predispositions to atopic dermatitis will more or less apply to BOG. The affected dogs are adult (3 to 10 years) and have suffered chronic dermatitis for years.
The chief complaints are pruritus and an offensive odour. The lesions include erythema, lichenification and hyperpigmentation, seborrhoea oleosa, excoriations and self-induced alopecia. They may be localized (cranial aspect of the neck, axillae, ventrum) or generalized. Associated otitis externa is common. Usually, there is no lesion of pyoderma associated with BOG (no papules, pustules, epidermal collarettes or crusts).
Diagnosis of BOG is based on history, physical examination, cytology, bacteriology, dermatopathology and response to therapy.
Cytology is the most useful technique to demonstrate BOG. The tape strip technique is the most appropriate. A rapid staining is done and microscopic examination shows numerous colonies of cocci. These can also be found in sites without lesions, indicating that the BOG is more widespread than the lesions might suggest, being in fact a more or less generalized condition.
Bacteriological cultures can be done using a swab that is rolled onto the skin, but this is usually done only in severe cases, when cytology shows rods (rare) and/or in case of poor response to therapy.
Dermatopathology shows a non-specific mild to moderate superficial, perivascular, sometimes interstitial, irregular hyperplastic and spongiotic dermatitis, in both affected and non-affected areas. Cocci may be observed in the stratum corneum but their absence should not rule out the disease (perhaps because of a non-linear distribution of the organisms and/or by the removal of the stratum corneum during the processing). SLAM and pigmentary incontinence can be seen. No lesions of pyoderma are observed. In fact, dermatopathology is less useful than cytology to establish the diagnosis of BOG.
Response to therapy is the ultimate diagnostic criterion.
Differential diagnosis includes all dermatitis with pruritus and seborrhoea, including ectoparasitic and allergic skin diseases, as well as Malassezia dermatitis. In fact BOG and MOG can be clinically and cytologically associated, and both can be secondary to allergic skin diseases, particularly atopic dermatitis.
Systemic therapy is indicated as for pyoderma. Appropriate antibiotics should be selected based on appropriate kinetics and good cutaneous penetration, activity against staphylococci, bactericidal activity rather than bacteriostatic activity particularly in severe cases, easy administration (oral, q12h or q24h), absence of secondary effects, and reasonable cost. The choice is most often empirical: cephalexin, Clavamox, trimethoprim-sulfa, fluoroquinolones, or clindamycin. The use of cephalexin at a dose of 30 mg kg-1 divided bid during 28 days, without associated topical therapy, was effective in a group of 8 dogs, significantly decreasing both the cutaneous and mucosal staphylococci populations and also the cutaneous signs. An interesting finding was that the staphylococci populations were not completely eliminated, but rather reduced, closer to that of the normal flora of healthy dogs (Pin, Carlotti et al, 2006).
Topical therapy is beneficial in canine BOG. Clipping may be useful, at least in the most severely affected areas. The main useful topical products are chlorhexidine (lotion and/or shampoo), povidone-iodine (lotion and/or shampoo), benzoyl peroxide (shampoo and eventually gel), and ethyl lactate (shampoo). They should be used frequently, e.g., once a day, at the beginning of therapy. Later, frequency of application may decrease. It is justified to treat BOG with compounds that decrease microbial adherence and increase the production of antimicrobial peptides, along with specific antimicrobial therapy.
Topical or systemic glucocorticoids should never be used in BOG, even in case of severe pruritus, because they can perpetuate the disease and cause severe relapses ("rebound effect").
The patients should be treated for one month at least and an appropriate follow-up is very important. This allows performing both a clinical and a cytological evaluation of the response to therapy. If a certain level of pruritus is still present an underlying pruritic dermatosis should be suspected (parasitic or allergic in origin) whereas if the animal remains seborrhoeic without pruritus, an underlying cause of seborrhoea should be envisaged, such as an endocrine disorder. Therapy of an underlying skin disease is obviously mandatory and prevents relapses.
MOG (Malassezia dermatitis) and perhaps BOG are relatively common skin diseases in dogs and can mimic and be secondary to a number of other dermatoses. They may be associated with one another. Cytological examination and an appropriate systemic treatment should be used to confirm the diagnosis. In all cases, an underlying cause should be considered. However, there is no doubt idiopathic ("primary") MOG and BOG exists.
References are available upon request.