Cushing‘s syndrome (hypercortisolism) is rare in guinea pigs. Due to a higher frequency of pulsatile ACTH release, the basal blood cortisol concentration in guinea pigs is several times higher than in dogs and cats. Hence the term hypercortisolism is used in English literature. In addition to adrenal Cushing‘s disease, the pituitary form has also been described. Typical clinical signs are alopecia without pruritus, polydipsia/polyuria, polyphagia, truncal obesity and, as the disease progresses, bilateral exophthalmos, skin atrophy and hyperpigmentation, weight loss and muscle atrophy. Due to the low prevalence, other possible causes should be excluded first. Urinalysis (specific gravity, biochemistry and sediment if necessary), haematology and blood biochemistry are prerequisites. High basal cortisol concentrations are physiological in guinea pigs and may increase due to stress, handling, illness, pregnancy and/or vitamin C deficiency (- 1500 ng/ml). In animals with Cushing‘s disease, cortisol concentrations can reach up to 3500 ng/ml causing determination cortisol in the blood only possible with extensive dilution. Determination of cortisol concentration in saliva may be a good alternative in these cases, as the cortisol concentration in saliva is usually much lower than in blood, and stress-related concentration fluctuations do not occur as quickly. Saliva sampling is described as non-invasive and stress-free, which may not be entirely accurate. Although compared to blood sampling by an inexperienced veterinarian, saliva sampling is less stressful. Contamination of saliva with blood leads to falsely high cortisol concentrations. Salivettes® (Fig. 1) should be used because of their larger sample volume and higher sensitivity. A dexamethasone suppression test (basal sample, subcutaneous low dose 0.01 mg/kg or high dose 0.1 mg/kg dexamethasone, sampling at 4 and 8 hours) is well suited for differentiating between adrenal and pituitary causes. However, no reference values are available for blood or saliva, except in guinea pig saliva, so assessment is based on the dog‘s values. The ACTH stimulation test (baseline sample, 20 I.U. ACTH/animal i.m. and sampling at 4 hours) is, as in dogs, mainly suitable for treatment monitoring.
There are few reported cases of Cushing‘s syndrome in hamsters, with non-pruritic alopecia and polydipsia/polyuria (three teddy hamsters and one golden hamster). Laboratory diagnostic tests have not been established for this species. With a low urine specific gravity, an ultrasound examination of the adrenal glands may be helpful for diagnosis. However, a definitive diagnosis can so far only be made by histopathological study of the affected adrenal glands.

Hyperadrenocorticism (HAC) is relatively common in ferrets. The prevalence varies according to the region and population studied. A US study in 94 ferrets attending a specialised veterinary practice showed a prevalence of 20-25%. In another study in the Netherlands with 1,274 animals, the prevalence was only 0.55%. The onset of clinical signs is on average 3.5 years after castration. There is no sexual predisposition according to the literature. Adrenal lesions are nodular hyperplasia (56%), adenocarcinoma (26%) or adenoma (16%), which are mostly (84%) unilateral. Besides melatonin deficiency in indoor housing (altered day-night rhythm, longer daylight duration) with loss of inhibitory effect on the hypothalamus (GnRH), neutering is considered the main cause of HAC. The lack of negative feedback of gonadal steroids after neutering leads to a permanently high gonadotropin (GnRH) concentration. This stimulates the pituitary gland to secrete LH/FSH, which in turn stimulates the zona reticularis of the adrenal cortex to produce steroid hormones, especially 17-OH-progesterone, oestradiol and/ or androstenedione (Fig. 2). Typical clinical signs are symmetrical alopecia beginning at the base of the tail and extending over the back, with pruritus in up to 40% of affected animals, and behavioural changes such as the reappearance of sex-specific behaviour and aggressiveness. In females, oestrogen production causes enlargement of the vulva, whereas males are more likely to present with dysuria due to androgenrelated prostatic changes (periprostatic and periurethral cysts). Diagnosis is made by clinical examination, ultrasound and blood tests (Adrenal profile ferrets). With the analysis of 17-OH-progesterone, oestradiol and androstenedione in this profile, the diagnostic sensitivity increases to 96%. An increase in the concentration of at least one of these hormones above the reference range is indicative of HAC.

Diseases of sexual glands

Alopecia may also be caused by diseases of the sexual glands, such as ovarian cysts in guinea pigs or neoplasms causing paraneoplastic syndrome. Hyperestrogenism occurs in intact female ferrets, in animals with ovarian remnant syndrome (ORS) and in spayed female ferrets with HAC, resulting in increased oestrogen levels. Since female ferrets have seasonal polyoestrous and induced ovulation, a prolonged oestrus (standing oestrus) and corresponding hyperestrogenism can occur in the absence of mating and a daylight length of more than twelve hours. This results in bone marrow suppression with pancytopenia that can lead to life-threatening anaemia with thrombocytopenia. In neutered females with ORS and in animals of both sexes with HAC, the bone marrow suppression is rather mild. Typical clinical signs are vulval swelling (Fig. 3) and, in animals with HAC and ORS, symmetrical bilateral alopecia beginning at the base of the tail and spreading cranially. Rarely, galactorrhoea and gynaecomastia are observed. Pale mucous membranes are a sign of anaemia, petechiae of thrombocytopenia due to bone marrow suppression. Melena, haematuria and other haemorrhages may also occur. The diagnosis can often be made on the basis of clinical signs together with nonregenerative anaemia and later pancytopenia (thrombocytopenia, leukopenia) and the determination of oestradiol concentration. An ultrasound examination is useful for differentiation from HAC or ORS. In the case of permanent rancidity or ORS, diagnostic therapy with HCG (2 x at intervals of 14 days) leads to swelling of the vulva. Diagnosis can often be made on the basis of clinical signs, together with non-regenerative anaemia and subsequent pancytopenia (thrombocytopenia, leukopenia) and determination of oestradiol concentration. An ultrasound examination is useful to differentiate HAC or ORS. In case of permanent or ORS, diagnostic therapy with HCG (twice at 14-day intervals) causes swelling of the vulva. Ovarian cysts are prevalent in guinea pigs (up to 90%) and can be unilateral or bilateral. The number and size of ovarian cysts increase with age. Females without a male seem to be affected more often.
There are a distinction between rete ovarii, follicular and parovarian cysts, with rete ovarii cysts predominating. The cysts can be hormone-producing. Increased oestrogen production leads to bilateral flank alopecia, and some females in permanent heat are more aggressive. Due to fluctuating oestradiol concentrations in non-spayed animals and the lack of reference values, oestradiol concentration does not help detect hyperestrogenism. Therefore, the diagnosis is made by clinical improvement (hair growth and behavioural change) after HCG injection.

Conclusion

Endocrine diseases can lead to dermatological alterations such as alopecia with or without pruritus. These diseases are much less frequent than parasitic or infectious diseases as a
cause of skin lesions, hence the importance of ruling out these diseases before investigating endocrine causes.

Jana Liebscher, Dr Jutta Hein

Superficial pyodermas:

a. Impetigo appears with pustules usually located exclusively on the abdomen of puppies. A similar but severe process can be seen in immunosuppressed older dogs with large flaccid or tense pustules (bullous impetigo).

b. Bacterial folliculitis is the most common form of canine pyoderma and affects the hair follicle producing focal, multifocal or generalised alopecia with the possible presence of papules, pustules, crusts and epidermal collarettes. It is accompanied by itching regardless of the primary cause.

c. Superficial spreading pyoderma is characterised by papules, pustules and epidermal collarettes. Epidermal collarettes can be very large with severe erythema and peripheral exfoliation. The infection causes pruritus in the affected area (Fig. 3).

d. Mucocutaneous pyoderma presents with depigmentation progressing to erosion-ulceration and crusting. It is located in mucocutaneous junctions, mainly on the lips, but it can also appear on the nose, eyelids, vulva, foreskin and anus. Its principal differential diagnoses are discoid lupus erythematosus (DLE) and cutaneous epitheliotrophic lymphoma (CEL), hence the importance of a correct diagnosis since the prognosis and treatment of these three diseases is totally different. Diagnosis is based on clinical presentation and skin biopsy. Prior to biopsy sampling, pretreatment with systemic antibiotics for at least one week is recommended to reduce histopathological lesions associated with a possible secondary bacterial complication in the case of DLE and CEL (Fig. 4).

If pustules are present, diagnosis is based on the clinical presentation and the cytology, in which the presence of bacteria inside the neutrophils will be observed. Cases of bacterial folliculitis without pustules or epidermal collarettes are challenging to diagnose, as only a biopsy can give certainty of diagnosis. The main differential diagnoses of bacterial folliculitis are demodicosis and dermatophytes. So the diagnostic protocol requires trichography to check for the presence of follicular casts (indicating inflammation of the follicle) and the absence of Demodex (ruling out demodicosis), and fungal elements or destruction of the hair shaft structure. If dermatophytosis is the main suspicion, dermatophyte culture or dermatophyte PCR should be performed.

The use of topical antiseptics, preferably in the form of baths, is usually sufficient to treat juvenile impetigo.
The other superficial pyodermas require topical treatment with antiseptics and systemic antibiotic treatment when they are generalised. Localised lesions can respond to antiseptic treatment alone and add topical antibiotics if necessary.

Mucocutaneous pyoderma is a curious process since it requires a very long antibiotic treatment despite being a superficial pyoderma.

Deep pyodermas:

a. Furunculosis. When bacterial infection severely affects the hair follicles, hair follicle rupture or furunculosis occurs. This results in the extension of the infection into the mid and deep dermis and a foreign body reaction associated with the release of hair and keratin into the dermis, producing pyogranulomatous lesions that clinically manifest with nodules, draining tracts, ulcers and crusts.

b. Abscesses are encapsulated collections of pus and necrotic tissue, clinically manifested as erythematous, hot and painful lumps. Usually caused by penetration of bacterial agents through puncture wounds or bites.

c. Cellulitis is diffuse infection and inflammation through tissue planes, usually regional, although it can occur circumscribed. It occurs with swelling, pain and heat. Attention to juvenile cellulitis, which is not an infectious but an immune-mediated process that requires treatment with antiinflammatory/immunosuppressive drugs.

Diagnosis of deep pyodermas is based on the clinical picture, cytology, biopsy and bacterial culture of dermal tissue.
Cytology of furunculosis shows a pyogranulomatous inflammatory reaction due to the foreign body reaction generated by the rupture of hair follicles with mainly neutrophils and macrophages, usually with an eosinophilic component (Fig. 5).

Bacteria are not easily observed within these cytologies. In the case of abscesses, the inflammation is neutrophilic with numerous intra- and extracellular bacteria being observed on cytology examination.

Treatment of deep pyodermas requires the use of systemic antibiotics based on culture and bacterial sensitivity. Abscesses require surgical drainage together with antibiotic therapy.

The duration of antibiotic treatment will depend on the depth of the infection. Superficial pyodermas usually require 3-4 weeks of treatment, deep pyodermas a minimum of 6-8 weeks. Once the clinical cure (complete absence of lesions) has been achieved, treatment should be maintained for a further seven days for superficial infections and at least 14 days for deep infections.

The main bacterial agent in canine pyoderma is Staphylococcus pseudointermedius. Therefore in case of a first episode of non-life-threatening skin infection, with clinical lesions and cytology consistent with superficial pyoderma, where there is no reason to suspect bacterial resistance, treatment with first generation cephalosporins or amoxicillin/clavulanic acid can be selected empirically.
Warning: never use second-line antibiotics (e.g. quinolones) or third-line without a culture and bacterial susceptibility test. Indiscriminate use of antibiotics is negligent and leads to the development of bacterial resistance.

Bacterial culture and sensitivity are necessary whenever any of the following applies:

• Deep pyoderma or life-threatening infections
• No consistency between clinical signs and cytology
• Rod-shaped bacteria on cytology
• Infections not resolving with empirical antibiotic therapy
• Immunosuppressive disease or treatment
• Non-healing wounds
• Post-surgical or nosocomial infections

In general, most pyodermas are secondary to another dermatological or primary systemic disease, which must be investigated, diagnosed and treated to avoid the recurrence of the process. The diseases that most frequently induce the appearance of pyodermas are allergic diseases, it is also common in endocrine disorders such as hypothyroidism and hyperadrenocorticism. But any skin disease can trigger bacterial growth and establish a secondary bacterial infection.

Primary and idiopathic recurrent pyodermas are rare, and their diagnosis is based on ruling out any probable primary disease. Idiopathic recurrent pyoderma often requires prolonged antibiotic therapy and tailored management regimens to prevent recurrences.

Dr Carmen Lorente, DVM, PhD, DipECVD