Reports of dermatitis caused by apicomplexan protozoa with intralesional parasites are rare in the cat. The best-known entity is dermatitis associated with T. gondii. In a case series consisting of 100 histologically confirmed feline clinical cases of toxoplasmosis, two cases out of 100 involved skin lesions, but T. gondii were not present intralesionally [7]. One disseminated toxoplasmosis case was reported with multiple cutaneous nodules [8], a second case with a single nodule with necrotizing inflammation affecting the skin and mammary tissue [9], and the third case with cutaneous ulcers and hyperemic nodules [10]. In all cases, intralesional T. gondii organisms were detected. As an experimental infection has shown that Neospora caninum can cause a generalized disease in the cat [11], N. caninum is invariably referred to as a possible causative agent when tachyzoites are found in inflamed feline skin. The possibility of N. caninum must be considered, as most case reports note positivity, and hence, cross-reactivity, for both anti-T. gondii and anti-N. caninum antibodies in immunohistochemistry and serology. In addition, one feline case has been described with a disseminated protozoal infection with nodular skin lesions and intralesional tachyzoites. As the organisms exhibited morphologic characteristics of both N. caninum and T. gondii, they were referred to as T. gondii-like organisms [12]. These cases resemble the clinical presentation, histological, cytological, and TEM findings of the present case.
The parasites of the genus Caryospora are coccidian intracellular intestinal parasites among reptiles and raptorial birds. Caryospora may utilize primary hosts' prey animals as secondary hosts [1, 2]. The source of the infection in the present case remains unknown. Caryspora bigenetica infection has not been previously documented in Finland. Only two snake species occur in Finnish mainland wildlife: a viper (Vipera berus) and a grass snake (Natrix natrix). They are common and widespread in Finland, but their intestinal parasites have not been studied. However, several Viperidae species may serve as hosts for Caryospora spp. [1]. Experimental infections have shown that the secondary hosts may acquire the infection from oocysts voided by the snake (primary host) or by consuming infected secondary hosts bearing caryocysts [1, 3]. Hence, the kitten may have gained the infection feco-orally (snake-to-kitten route) or by ingesting a secondary host (snake-to-mouse-to-kitten route). Also, an unlikely transplacental and galactogenic infection from the queen transmitted to the kitten (snake/mouse-to-dam-to-kitten route) is possible, although the queen and the sibling showed no signs of infection. Figure 5 illustrates the life cycle stages occurring in the secondary host.
If the parasite’s mouse-to-snake cycle played an essential role in nature and secondary hosts could get infected by consuming an infected mouse, we should see feline cases more often, as is the case with feline T. gondii, Toxocara cati, and Isospora spp. infections. The lack of earlier case reports suggests that C. bigenetica is presumably an opportunistic pathogen requiring an immunocompromised cat to manifest infection.
The disease progression from single nodular skin lesions to severely debilitating and deforming skin disease was rapid. Young age may predispose to C. bigenetica infection, as seen in dogs [4, 5]. Injecting a long-acting corticosteroid after disease onset may have affected the clinical course, as has been shown in cats experimentally infected with N. caninum [10]. However, it is unlikely that the age or the stress of being a stray cat caused significant immunosuppression to result in such a rare and severe disease; hence, an unnoticed immunodeficiency was suspected.
Clinical differential diagnoses considered were a deep bacterial, fungal, or protozoal infection. The bacterial culture yielded A. nosocomialis. Fatal infection with Acinetobacter baumannii has been reported in a cat [13]. In the present case, A. nosocomialis was considered a cause of secondary infection.
The skin lesions of the feline case described here resembled the C. bigenetica-associated lesions reported in other species. Infection with C. bigenetica in a puppy resulted in multifocal non-alopecic papules and nodules on the head, trunk, and limbs. The pinnae, periorbital region, and muzzle were affected [4]. In an experimental study, mice inoculated with oocysts exhibited swollen muzzles, footpads, scrota (males), partially closed eyelids, and lethargy 8 days after infection [3]. In the same study, infected pigs displayed erythematous eyelids, followed by cutaneous erythema and edema, and all pigs appeared lethargic [3].
The definitive species identification required sequencing of the PCR product. At the 18 S locus, the present isolate exhibited 100% homology without gaps with the Caryospora cf. bigenetica strain, and the molecular diagnosis was considered certain.
Had PCR and sequencing been unavailable, the abundance of unsporulated oocysts and caryocysts and the parasite's effective reproduction within macrophages and several other cell types comprised findings that might have allowed differentiation from other protozoal infections and a presumptive diagnosis based on cytology or histopathology. In the histological sections studied, almost all macrophages contained protozoa. Detecting mature tachyzoites enabled narrowing the differential diagnoses to apicomplexan protozoa, T. gondii, and N. caninum as the most likely protozoa. However, the zoites were sparse in the present case, the smaller immature merozoites in macrophages resembled Leishmania’s amastigotes, and unsporulated oocysts resembled Coccidioides’ spherules; hence, several infectious differential diagnoses had to be considered.
On TEM, the ultrastructural morphology of the zoites was typical of apicomplexan coccidian protozoa, but TEM did not allow species- or genus-level identification. The number of rhoptries in the tachyzoites varied but finding parasites primarily within membrane-bound vacuoles in the host cells was an ultrastructural feature resembling more T. gondii than N. caninum [14].
Therapy with a moderately high dose of clindamycin was initiated due to suspicion of Toxoplasma gondii-like protozoal infection. A young Rottweiler with cutaneous caryosporosis responded to clindamycin 20 mg/kg and trimethoprim-sulfamethoxazole 23 mg/kg PO q12h [5]. The disease relapsed after treatment was discontinued. Due to the rapid progression and delay in identifying the organism, further treatment modalities were not commenced in this case.
The case described within adds one more apicomplexan parasite to the list of causative agents of protozoal dermatitis in cats and shows that the cat can serve as a secondary host for C. bigenetica.