Introduction

Norwegian or crusted scabies (N/CS), caused by Sarcoptes scabiei, is a rare disease in medical and veterinary dermatology. In humans, it has been mainly associated with cell-mediated immunosuppression induced by human immunodeficiency virus infection, autoimmune diseases, immunosuppressive diseases or treatment, mental deficiency, old age, or genetic predisposition.^1–6

N/CS has been described in the dog and the cat, but very few animal cases have been reported.^7–10 This type of sarcoptic mange differs from ordinary scabies (OS) by the high number of mites demonstrated in skin scrapings, the absence or low intensity of pruritus, and the formation of very thick parakeratotic crusts.^11,12 Immunosuppressive disease or medication is usually identified as an underlying cause.^7–10,13

This article describes two new canine N/CS cases with concomitant symptomatic canine leishmaniosis (CanL) and their response to a combined miticidal and antileishmanial treatment. It is assumed that the manifestation of N/CS in these cases was the result of cell-mediated immunosuppression, most likely induced by leishmaniosis and malnutrition.

Case Report

Case 1

A 4 yr old, intact male, stray Siberian husky mixed-breed dog that was recently rescued by an animal shelter was admitted in our clinic due to nonpruritic skin lesions of a 15-day duration and rapid loss of body weight. The dog appeared emaciated (2/9 body condition score) with pale mucous membranes, peripheral lymphadenomegaly, and enophthalmos. Deep ulcers were observed over several bony prominences of the limbs along with thick, fissured, greasy adherent crusts over the ventrum, elbows and periocular area, ear margins, and nasal bridge (Figures 1A, B), as well as partial alopecia, erythema and/or hyperpigmentation, lichenification, papules, psoriasiform scales, and a few epidermal collarettes. The pinnal-pedal reflex was weak positive, but there were no other signs of pruritus. Complete blood count, serum biochemistry, and urinalysis revealed a nonregenerative anemia (packed cell volume [PCV] = 21%, reference range [ref]: 37–55%), hyperproteinemia (9.6 g/dL, ref: 6.0–8.0 g/dL), and proteinuria (urine protein/creatinine ratio [UP/C] = 3.2, ref ≤ 0.2). Leishmaniosis was diagnosed by immunofluorescent antibody test (IFA) (1/1600: cutoff value 1/50) and lymph node fine needle aspiration cytology. The microscopic examination of superficial skin scrapings revealed high numbers of Sarcoptes mites in all developmental stages (≥5 per lower power field). The dog was hospitalized in an isolated ward and treated with intravenous fluids and electrolytes^a, parenteral antibiotics (cefoxitin^b) at the dose of 30 mg/kg q 8 hr, and oral allopourinol^c at the dose of 10 mg/kg q 12 hr, along with daily baths with antibacterial (chlorhexidine^d) and antiseborrheic (ammonium lactate and piroctone olamine^e) shampoos. A remarkable clinical improvement was witnessed after 2 wk along with a slight PVC (26.8%) increase, and the dog was discharged on oral cefadroxil^f at the dose of 30 mg/kg q 12 hr for 4 wk, together with antileishmanial medication comprised of meglumine antimoniate^g at the dose of 100 mg/kg subcutaneously q 24 hr for 30 consecutive days, and oral allopourinol at 10 mg/kg q 12 hr until the negativity of IFA titre. Scabies was treated with ivermectin^h (400 μg/kg) given subcutaneously biweekly, 4 times, with the first injection given on the first day of hospitalization. Skin scrapings taken 2 mo after the admittance were negative for Sarcoptes mites. Complete resolution of the skin lesions and haircoat regrowth were noticed within 7 mo. Unfortunately, the dog died after another 5 mo because of CanL-associated end-stage kidney disease (International Renal Interest Society stage IV).

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Case 2

A 2 yr old intact male mixed-breed dog was admitted to our clinic 2 yr after the first case, by the same animal shelter in which he was being kept for the last 2 wk, with emaciation (2/9), generalized nonpruritic, and partial to complete alopecia, along with papules, psoriasiform scales and thick nonadherent crusts, hyperpigmentation, lichenification, and wrinkling of the skin (Figure 2A), deep ulcers localized over the pinnal tips and bony prominences of the hind limbs, and onychogryposis. On complete blood count examination and serum biochemistry, a nonregenerative anemia (PCV = 19%), lymphocytopenia (0.86 x 10³ ul), and a marginal hyperproteinemia (total solids = 8.2 g/dl) were found, respectively. Urinalysis revealed severe proteinuria (UP/C = 4.2) and low specific gravity (specific gravity urine = 1,015). Leishmaniosis was diagnosed by IFA (1/1600) and lymph node fine needle aspiration cytology. High numbers of Sarcoptes mites in all developmental stages were found on the multiple superficial skin scrapings (Figure 2B). Scabies was treated with selamectinⁱ spot-on formulation, applied biweekly at the dose of 7 mg/kg for a total of six treatments, in combination with a twice weekly application of an antiseborrheic shampoo (phytosphingosine^j). Antileishmanial treatment was the same as had been applied in case 1. In addition, oral enalapril maleate^k at the dose of 1 mg/kg q 24 hr and a renal clinical diet^l were prescribed. By the fifth month of treatment, and the dog still on allopourinol, all skin lesions except for the ulcers on the pinnal tips had disappeared, body condition was improved (5/9), PCV was increased (27.5%), and proteinuria was decreased (UP/C = 1.2), whereas lymph node cytology was negative for Leishmania amastigotes and skin scrapings were negative for Sarcoptes mites. Due to the still high IFA titre (1/800), repetition of the treatment with meglumine antimoniate was decided. On the last communication with his new owners 1 yr later, we were informed that the dog was clinically healthy but still kept on allopurinol.

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Discussion

This clinical study involves two genetically unrelated stray dogs with N/CS, the development of which could be attributed to concurrent symptomatic leishmaniosis and malnutrition.

This lifestyle as well as the lack of vaccinations and antiparasitic medications most likely predisposes a dog to infectious (e.g., leishmaniosis, canine distemper) and/or parasitic diseases (e.g., sarcoptic mange), which are quite common in Greece.^14,15 The three already reported canine N/CS cases were owned dogs, the underlying immunosuppression of which was attributed to hyperadrenocorticism, hypothyroidism, and to prolonged corticosteroid administration.^7,8,10 In the study of Leone et al, 10 out of 16 dogs with N/CS were suffering from one of seven different debilitating diseases, while the other six dogs were strays and debilitated, but no underlying disease was found.¹³ When no immunosuppressive disease or predisposing medication can be found, genetic and/or familiar factors are incriminated, as is the case with the Australian Aborgines.^2,6 Although not documented, it has been postulated that cocker spaniels are at increased risk to develop N/CS.¹¹ Interestingly, one of the three reported cases was a cocker spaniel, whereas neither of our two dogs was purebred.¹ The combination of malnutrition and leishmaniosis could be considered immunosuppressive enough for N/CS to develop. Presumably, in both of our cases, the protein deficit was aggravated by the severe asymptomatic proteinouria, as a result of the commonly observed immune-mediated glomeronephritis in dogs with leishmaniosis.^14,16 Although not documented, this nephropathy has also been associated with chronic scabietic cases.¹² Since the authors of this study have seen several leishmanial, but otherwise well-cared for and nourished, dogs develop OS, malnutrition may play a role in the pathogenesis of N/CS, perhaps due to decreased leptin production by adipocytes that may eventually lead to T-cell dysfunction.¹⁷

Lesional histopathology of human and canine OS is characterized by a mixed-cell inflammatory infiltrate, typical of a delayed cell-mediated immune reaction, the lymphocytic component of which is overwhelmed by CD4⁺ T cells.^6,18 However, in N/CS, the inflammatory skin response has been found to be dominated by CD8⁺ T cells, at least in humans.¹ It has been assumed that this selective skin-homing of cytotoxic (CD8⁺) T cells along with an absence of B cells in the dermis can explain, at least in part, the failure of the skin’s immune system to mount an effective response, resulting in the uncontrolled proliferation of the parasite.¹ CD8⁺ T-cell activation may also induce dysregulation of keratinocyte apoptosis that may explain the epidermal hyperproliferation.⁶ In the clinically similar exfoliative dermatitis of CanL, the dermal inflammatory infiltrate is also dominated by CD8⁺ T lymphocytes.¹⁹ In human N/CS, the strong T-cell upregulation of the antiinflammatory cytokine TGFβ in the scabietic lesions, the increased levels of IL-5 and IL-13 by the stimulated peripheral blood mononuclear cell (PBMC) (nonprotective Th2 reaction), and the hyperproliferation of T regulatory cells, along with the ensuing IL-10 secretion, belong to those immunosuppressive mechanisms that have been incriminated for the unrestricted proliferation of Sarcoptes mites within the excessively thickened stratum corneum.^6,18

In the less commonly seen feline sarcoptic mange, the interplay between the mites and the immunological response of the host also results in crusted lesions associated with minimal or absent pruritus and abundance of mites.⁹ Since the feline disease has been acquired from other animal species, it is assumed that the less-effective systemic and local immunity of the cat as a “new” host species favors the establishment of N/CS.⁹ Again, in the feline disease, the defective cell-mediated immunity plays a role, at least in part, in the development of such a severe crusting.⁹

The absence or the low intensity of pruritus in N/CS may also contribute to the excessive keratin build-up, in contrast to OS in which the frequent scratching removes a substantial number of mites.^3,10,16 In both of our cases, pruritus was actually absent, thus explaining the weak pinnal-pedal reflex elicited in case 1, although in up to 10–50% of the pruritic scabietic dogs, this reflex can be also negative.²⁰ However, these two different types of crusting have also been seen in people with N/SC.⁶ The more severe clinical picture of our cases compared to the reported ones could be attributed to the coexisting CanL, of which the contribution to crusting cannot be assessed due to the lack of histopathology, which is the main drawback of this study.^7,8,10

Eosinophilic lymphadenopathy, with or without peripheral eosinophilia, is a common finding in OS, raising the suspicion of the disease when no mites can be found, at least according to our experience. However, in our cases, eosinophilic counts were normal in the peripheral blood, as well as in two of the three canine cases already reported.^7,8 In the third case, eosinopenia was detected instead, most likely due to the underlying hyperadrenocorticism.¹⁰ At the same time, eosinophilic lymphadenopathy was absent in our dogs.

For a successful outcome in canine N/CS, the treatment should be focused on the complete elimination of the mites and the management of the underlying disease along with the adequate nutritional support. As humans, and probably dogs, with N/SC pose a higher risk for public health due to the extreme proliferation of mites, which benefit from the heavy crusting, the role of frequent antiseborrheic baths is pivotal in controlling the disease.^2,3

Conclusion

In conclusion, N/CS may appear in immunosuppressed dogs because of systemic diseases and malnutrition. Since the exfoliative skin lesions of CanL are overwhelmed by the more severe N/CS, search for the former and its role as an underlying factor for N/CS is mandatory, at least in the endemic areas.