Idiopathic systemic granulomatous disease

From Horse
Seven-year old Dutch Warmblood gelding with several firm non painful nodules varying in diameter between 5 and 15 cm between the forelimbs, on the neck, in the lumbar region and on the abdomen
Above horse, view of affected skin in the pectoral region
An 11-year-old Trakehner mare with generalized scaling and crusting on head, neck, and body resulting from sarcoidosis
Neck of above horse
Inguinal region of above horse
Swollen bronchial lymph nodes in a horses affected by generalized sarcoidosis

Idiopathic systemic granulomatous disease is an uncommon immune-mediated disease of horses. The disease is also known as sarcoidosis, equine idiopathic systemic granulomatous disease, generalised or granulomatous disease, systemic granulomatous disease, equine histiocytic disease and equine histiocytic dermatitis[1].

Equine idiopathic systemic granulomatous disease is characterized by exfoliative dermatitis, severe wasting, and granulomatous inflammation of multiple organ systems[2]. Skin lesions take two forms, with the more common being scaling, crusting, and alopecia[3]. The lesions usually start on the face or legs before progressing to generalized disease. Affected horses may have bilaterally symmetric lesions over the jugular furrow[4].

Cause

The cause of the disease in horses is unknown. Many similarities to human sarcoidosis can be found.

Too few cases of equine idiopathic systemic gran­ulomatous disease have been reported to allow valid genetic, infectious, or environmental associations to be made. The disease may be more common in the western United States, as are mycobacterial diseases in general. This has led to speculation that mycobacteria may play a role in the equine disease as well as in the human equivalent. In a series of four cases, three horses had positive Borrelia spp titers, with Borrelia spp DNA identified in one horse[5]. The significance of this is unclear because the prevalence of positive Borrelia spp titers exceeds 20% of horses in endemic areas, and clinical illness associated with Borrelia burgdorferi infection is uncommon in horses[6]. In a recent retrospective study of cutaneous equine sarcoidosis, PCR assays on paraffin-embedded specimens from eight horses were negative for Mycobacteria spp, B. burgdorferi, Coccidioides immitis, Cryptococcus neoformans, and Corynebacterium pseudotuberculosis[7].

Similar lesions have also been found in cattle with naturally occurring and experimentally induced hairy vetch (Vicia spp) toxicosis. The disease in cattle may be caused by vetch resulting from hypersensitivity to one or more plant constituents that induces the immunologic reaction[8]. Similar generalized granulomatous disease has been found in horses that have ingested hairy vetch, but there has been no documented exposure to the plant in most reports[9].

Because neither culturing nor electron microscopy has revealed viral, bacterial, or fungal organisms, it is likely that idiopathic systemic granulomatous disease occurs because of an abnormal host immune response to either an ingested or inhaled environmental antigen or an underlying infectious or neoplastic process resulting in chronic antigenic stimulation[10].

Clinical signs

Skin lesions may rarely include nodules or large tumor-like masses. Most affected horses develop exercise intolerance, weight loss, and a low-grade fever. Many affected horses also have internal organ involvement confirmed at necropsy, which would explain the wasting syndrome. Clinical signs vary, depending on the internal organ involved. The following (listed in order of decreasing frequency) may be affected: the lungs, lymph nodes, liver, gastrointestinal tract, spleen, kidneys, bones, and central nervous system. The onset of the disease may be insidious or explosive, but typically the clinical course is slowly progressive. The equine disease is more severe than human sarcoidosis.

Non cutaneous clinical signs of sarcoidosis in horses indicating systemic involvement include weight loss, anorexia, respiratory distress, peripheral lymphadenopathy, fever and exercise intolerance.

More common causes of scaling and crusting dermatoses must first be considered in horses with extensive exfoliative dermatitis, especially in horses presenting without signs of wasting and systemic disease. Common infectious diseases, such as dermatophilosis and dermatophytosis, should be ruled out. Less common diagnostic differentials include idiopathic seborrhea, drug reaction, contact dermatitis, pemphigus foliaceus, cutaneous and systemic lupus erythematosus, epitheliotropic lymphoma, multisystemic eosinophilic epitheliotropic disease, and toxicoses caused by arsenic, mercury, selenium, or iodide.

Diagnosis

The diagnostic workup should include a complete blood count (CBC), fibrinogen level testing, a serum chemistry profile, and either radiography or abdominal ultrasonography, depending on the clinical signs. The CBC and serum chemistry profile results may be normal, although some affected horses have leukocytosis, mild nonregenerative anemia, hyperfibrinogenemia, hyperglobulinemia, and hypoalbuminemia.5 Thoracic radiography, abdominal ultrasonography, and percutaneous needle biopsies of the lungs and/or liver may be helpful in determining the presence and extent of systemic involvement. In horses with lung involvement, findings on thoracic radiographs may include interstitial infiltration.

Multiple, full-thickness punch biopsies of the affected skin and peripheral lymph nodes should be performed. Biopsy specimens should be examined by a pathologist experienced in interpreting equine skin biopsy results. The major histologic changes are aggregates of epithelioid cells and multinucleated giant cells (i.e., sarcoidal granulomas). Granulomas in the skin tend to be in the superficial and perifollicular dermis.

A diagnosis of idiopathic systemic granulomatous disease is confirmed when typical granulomatous changes are found on biopsy and other granulomatous diseases caused by fungal or bacterial agents are ruled out by culture or special stains.

Treatment

Response to therapy is not well documented because of the small number of case reports in the literature and the variable clinical course. The prognosis varies with chronicity and severity of the disease.

Administration of corticosteroids is the preferred treatment. Immunosuppressive doses of glucocorticoids may be effective if administered early in the course of the disease before the onset of wasting. Recommended drugs and doses include prednisolone at 2 to 4 mg/kg PO q24h or dexamethasone at 0.2 to 0.4 mg/kg PO q24h.

Prednisolone is preferred over prednisone in horses as shown in a recent study reporting reduced efficacy of prednisone due to poor absorption and lack of production of the active metabolite prednisolone[11]. Cortico­steroid therapy should be continued for several weeks to months with a slow taper when remission of clinical signs is achieved. There are a few reports of spontaneous remission or successful treatment with prednisolone. In a recent retrospective study, three of nine horses were euthanized soon after diagnosis, with the others surviving as long as 12 years. Of the six that survived, four had only cutaneous lesions, and the disease resolved without specific treatment in the other two horses[12].

It appears that horses with only cutaneous involvement have a better long-term prognosis. In less severe cases or cases that appear to regress, a single antigen trigger may no longer be present and/or the host immune response may be less reactive. Aggressive immunosuppression is probably warranted in most cases. However, the relative benefits and risks of long-term corticosteroid therapy should be weighed in cases with only cutaneous involvement because they may resolve with more conservative management.

References

  1. Sellers RS, Toribio RE, Blomme EA (2001) Idiopathic systemic granulomatous disease and macrophage expression of PTHrP in a miniature pony. J Comp Pathol 125:214-218
  2. Scott DW (2003) Equine Dermatology. St. Louis, WB Saunders, pp:675-680
  3. von Tscharner C, Kunkle G, Yager J (eds) (2000) Stannard's illustrated equine dermatology notes: Immunologic diseases. Vet Dermatol 11(3):170-172
  4. Axon JE, Robinson P, Lucas J (2004) Generalized granulomatous disease in a horse. Aust Vet J 82(1&2):48-51
  5. Rose JF, Littlewood JD, Smith K, et al (1998) A series of four cases of generalized granulomatous disease in the horse, in Kwochka KW, Willemse T, von Tscharner C (eds): Advances in Veterinary Dermatology III. Boston, Butterworth-Heinemann, pp:562-563
  6. Fritz CL, Kjemtrupam AM (2003) Lyme borreliosis. JAVMA 223(9):1261-1270
  7. Spiegel IB, White SD, Foley JE, et al (2007) A retrospective study of cutaneous equine sarcoidosis and its potential infectious aetiological agents. Vet Dermatol 17(1):51-62
  8. Johnson B, Moore J, Woods LW, et al (1992) Systemic granulomatous disease in cattle in California associated with grazing hairy vetch (Vicia villosa). J Vet Diagn Invest 4:360-362
  9. Anderson CA, Divers TJ (1983) Systemic granulomatous inflammation in a horse grazing hairy vetch. JAVMA 183(9):569-570
  10. Woods LW, Johnson B, Hietala SK, et al (1992) Systemic granulomatous disease in a horse grazing pasture containing vetch (Vicia sp). J Vet Diagn Invest 4:356-360
  11. Peroni DL, Stanley S, Kollias-Baker C, et al (2002) Prednisone per os is likely to have limited efficacy in horses. Equine Vet J 34(3):283-287
  12. Heath SE, Bell RJ, Clark EG, et al (1990) Idiopathic granulomatous disease involving the skin in a horse. JAVMA 197(10):1033-1036