diopathic systemic granulomatous disease isuncommon in horses. The disease is oftencalled sarcoidosis, as is human systemic granu-

lomatous disease, which has clinical and histo-pathologic similarities to the equine disorder.However, the term idiopathic systemic granuloma-tous disease is more accurate and avoids confu-

sion with equine sarcoids.1

Equine idiopathic systemic granulomatousdisease is characterized by exfoliative dermati-tis, severe wasting, and granulomatous inflam-mation of multiple organ systems.2 Skin lesionstake two forms, with the more common beingscaling, crusting, and alopecia.3 The lesions usu-ally start on the face or legs before progressingto generalized disease. Affected horses mayhave bilaterally symmetric lesions over thejugular furrow.4 Skin lesions may rarely includenodules or large tumor-like masses.3,4 Mostaffected horses develop exercise intolerance,weight loss, and a low-grade fever.2 Manyaffected horses also have internal organ involve-

January/February 2007 23 COMPENDIUM: EQUINE EDITION

Idiopathic SystemicGranulomatous Disease

Sandra J. Sargent, DVM, DACVDa

Benjamin R. Buchanan, DVM, DACVIM, DACVECCb

Linda A. Frank, MS, DVM, DACVD

Carla S. Sommardahl, DVM, PhD, DACVIM

Stephen A. Kania, MS, PhD

David S. Rotstein, DVM, DACVP

University of Tennessee

Send comments/questions via emaileditor@CompendiumEquine.comor fax 800-556-3288.

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ABSTRACT: Idiopathic systemic granulomatous disease in horses is characterized by exfoliative

dermatitis, severe wasting, and granulomatous inflammation of multiple organ systems. More common

causes of scaling and crusting dermatoses (e.g., dermatophilosis, dermatophytosis) must be ruled out in

making the diagnosis. Skin and peripheral lymph node biopsies have the greatest value in confirming

the diagnosis because of the ease of collection and likelihood of showing granulomatous changes. The

cause of the disease in horses is unknown but is likely an abnormal host immune response to an

antigen trigger. The preferred treatment is administration of corticosteroids, but the relative benefits

and risks must be weighed in horses with only cutaneous involvement. This article describes two

horses with primarily cutaneous manifestations of idiopathic systemic granulomatous disease. One

horse’s disease resolved after a short course of corticosteroid administration, but the other horse died

from suspected therapy-associated complications.

Article #1CE

aDr. Sargent is now affiliated withPittsburgh Veterinary Dermatol-ogy, Pittsburgh, Pennsylvania.bDr. Buchanan is now affiliatedwith Brazos Valley Equine Hos-pital, Navasota, Texas.

without signs of wasting and systemic disease. Commoninfectious diseases, such as dermatophilosis and der-matophytosis, should be ruled out. Less common diag-nostic differentials include idiopathic seborrhea, drugreaction, contact dermatitis, pemphigus foliaceus, cuta-neous and systemic lupus erythematosus, epitheliotropiclymphoma, multisystemic eosinophilic epitheliotropicdisease, and toxicoses caused by arsenic, mercury, sele-nium, or iodide.

DIAGNOSISThe diagnostic workup should include a complete

blood count (CBC), fibrinogen level testing, a serumchemistry profile, and either radiography or abdominalultrasonography, depending on the clinical signs. TheCBC and serum chemistry profile results may be nor-mal, although some affected horses have leukocytosis,mild nonregenerative anemia, hyperfibrinogenemia,hyperglobulinemia, and hypoalbuminemia.5 Thoracicradiography, abdominal ultrasonography, and percuta-neous needle biopsies of the lungs and/or liver may behelpful in determining the presence and extent of sys-temic involvement. In horses with lung involvement,findings on thoracic radiographs may include interstitialinfiltration.

Multiple, full-thickness punch biopsies of the affectedskin and peripheral lymph nodes should be performed.Biopsy specimens should be examined by a pathologistexperienced in interpreting equine skin biopsy results.The major histologic changes are aggregates of epithe-lioid cells and multinucleated giant cells (i.e., sarcoidalgranulomas). Granulomas in the skin tend to be in thesuperficial and perifollicular dermis.

A diagnosis of idiopathic systemic granulomatous dis-ease is confirmed when typical granulomatous changesare found on biopsy and other granulomatous diseasescaused by fungal or bacterial agents are ruled out by cul-ture or special stains.

CAUSEThe cause of the disease in horses is unknown. Many

similarities to human sarcoidosis can be found. Humansarcoidosis occurs worldwide and more frequently inwomen and some ethnic groups.6 Variation of preva-lence in geographic locations and populations suggeststhat ethnic susceptibility factors and environmental fac-tors underlie human sarcoidosis.7 In humans, surgical orposttraumatic scars and tattoos many years old maydevelop granulomatous reactions.7

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Idiopathic Systemic Granulomatous Disease24 CE

(text continues on p. 28)

• Idiopathic systemic granulomatous disease causesscaling and crusting that is often called sarcoidosis.

• Idiopathic systemic granulomatous disease likelyoccurs as a result of an abnormal host immuneresponse to an antigen trigger.

• Horses with only cutaneous involvement may have abetter prognosis, although aggressive treatment usingcorticosteroids can have severe adverse effects.

Key Points

ment confirmed at necropsy, which would explain thewasting syndrome. Clinical signs vary, depending on theinternal organ involved. The following (listed in order ofdecreasing frequency) may be affected: the lungs, lymphnodes, liver, gastrointestinal tract, spleen, kidneys,bones, and central nervous system.3 The onset of thedisease may be insidious or explosive, but typically theclinical course is slowly progressive. The equine diseaseis more severe than human sarcoidosis.3

More common causes of scaling and crusting der-matoses must first be considered in horses with exten-sive exfoliative dermatitis, especially in horses presenting

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Idiopathic Systemic Granulomatous Disease 25CE

Case OneA 24-year-old Thoroughbred gelding presented

with a several-month history of nonpruritic skin lesions.When the horse was purchased, patchy alopecia andscaling were present on the jugular furrows and face. Thelesions subsequently spread to the neck underneath themane, dorsal rump, lateral thorax, and abdomen. Thehorse’s attitude, appetite, and activity level were normal,and routine vaccinations were up to date.

During examination, the gelding had a normal bodycondition and appeared alert with no abnormalitiesother than skin disease and mild lymphadenopathy ofboth subiliac lymph nodes. Bilaterally symmetric,

Clinical Cases

multifocal, patchy alopecia with lichenification, scales,and crusts were found along both jugular furrows, thelateral thorax, the dorsal rump, and the dorsal neckbeneath the mane (A–D).

Surface cytology of samples from under crusts on the rump revealed many rods, cocci, and neutrophils,whereas skin cytology results from other sites wereunremarkable. Multiple deep and superficial skinscrapings tested negative for ectoparasites. Results of afungal culture were negative. Multiple punch biopsies of affected areas were obtained.

The CBC findings, serum chemistry profile results,and electrolyte and fibrinogen levels were within normal limits. Chest radiographs showed a focal heavybronchointerstitial pulmonary infiltrate within thecaudoventral lung and two mineralized opacities withinthe caudodorsal thorax. Ultrasonography of the liverrevealed a mild increase in echogenicity of the left lobe

A. A 24-year-old gelding (case one) with idiopathicsystemic granulomatous disease.

B. Extensive lesions on the left side.

C. Affected jugular furrow.

D. Close-up of exfoliative dermatitis on the lateralthorax.

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Idiopathic Systemic Granulomatous Disease26 CE

of the liver compared with that of the spleen, suggestingpossible cellular infiltrates. The changes could have beenage related but could also have been an indication ofbacterial infection, toxic insult, or chronic inflammation.

Results were negative for the following: aerobic, fungal,and mycobacterial culture as well as PCR analysis formycobacterial DNA in the skin, liver, and lymph nodes.Fresh tissue collected and submitted to the University ofCalifornia, Davisa for immunohistochemistry failed todetermine the lineage of the histiocytic cells in thedermis. Skin biopsies revealed moderate infiltrates ofmacrophages with lesser lymphocytes and occasionalmultinucleated giant cells in the dermis and around hairfollicles and adnexal structures (E, F). The diagnosis wassevere diffuse superficial and perifollicular granulomatous

Clinical Cases (continued)

G. Histopathology slide of a lymph node sample showinggranulomatous lymphadenitis and lymphoid hyperplasia.

aDr. V. K. Affolter, Department of Pathology, Microbiology, andImmunology, School of Veterinary Medicine, University of Cali-fornia, Davis.

F. Close-up of E showing a multinucleated giant cell.

E. Cutaneous histopathology slide showing superficialand perifollicular granulomatous dermatitis.

dermatitis. Biopsy of the liver showed diffuse, neutrophilicportal hepatitis; diffuse, moderate to marked periductularfibrosis; mild bridging fibrosis; and bile duct hyperplasiawith evidence of individual hepatocellular regeneration.Moderate to marked lymphoid hyperplasia was found inthe lymph node biopsy specimen. Accumulations ofmoderate numbers of epithelioid macrophages andmultinucleated giant cells were present in the lymphnode, resulting in a diagnosis of moderate granulomatouslymphadenitis and lymphoid hyperplasia (G). A diagnosisof idiopathic systemic granulomatous disease was madebased on the granulomatous changes found in the skinand lymph nodes.

Therapy with dexamethasone (0.1 mg/kg PO q24h)using the 2-mg/ml injectable form was dispensed. At the2-week recheck, the exfoliative dermatitis had markedlyimproved, with hair regrowth present in several areas of former alopecia (H, I). The lymph nodes were notpalpable, and the rest of the physical examination resultswere within normal limits. The owner was told to treatthe patient until clinical resolution before slowlytapering administration of dexamethasone, and a 1-month recheck was recommended.

After 27 days of dexamethasone therapy, the ownercalled to report that the horse had been acutely ill forless than 24 hours before being found dead in the stall.

During gross examination at necropsy, there wasfurther improvement in the skin lesions with only mildalopecia and hyperpigmentation remaining. There wasno microscopic evidence of granulomatous disease in theskin, suggesting a positive response to therapy. Bacterialand fungal pneumonia and bacterial pyelonephritis werefound. A meningioma was also found and wasconsidered an incidental finding.

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Case TwoA 12-year-old Tennessee walking horse stallion was

referred with a history of recent weight loss, decreasedappetite, nonpruritic skin lesions, and ventral edema. Theowner reported the onset of generalized papules and crusts1 to 2 weeks after annual vaccination for Venezuelan,Eastern, and Western equine encephalomyelitis as well astetanus. Scars from wounds that had occurred more than 2 years earlier had recently become more prominent withcrusts and scales on the surface. A weight loss of 50 to 70 lb(22.7 to 31.8 kg) had occurred over the previous 2 months.A noticeable decrease in appetite had also occurred over theprevious 2 weeks, with the onset of ventral abdominal andscrotal edema. The referring veterinarian had treated thepatient with ceftiofur and methylprednisolone acetateinjections, and improvements in the appetite and skinlesions were noted by the owner.

At presentation, the horse was in good bodycondition with no abnormalities other than skin diseaseand moderately severe pitting edema of the ventralabdomen. Multifocal areas of alopecia, crusts, and scalesconsistent with exfoliative dermatitis were especiallysevere along the ventral abdomen, on the neck along themane, and over the dorsal rump.

Results of a CBC, serum chemistry profile, andfibrinogen level testing were within normal limits.Results of multiple skin scrapings as well as bacterial and fungal skin cultures were negative. During gastricendoscopy, one healed lesion consistent with a previousgastric ulcer was seen. Ultrasonography of the scrotumshowed only edema with no evidence of herniation. Aherpesvirus titer was positive at 1:640, with a fourfoldrise demonstrated over a period of 7 days. An equineviral arteritis titer was negative at less than 1:4.

Multiple punch biopsy specimens of affected skinshowed moderate to severe infiltrates of macrophageswith lesser lymphocytes and moderate numbers ofmultinucleated giant cells in the dermis and around hair

Clinical Cases (continued)

follicles and adnexal structures. Focal replacement ofsebaceous glands by macrophages and multinucleatedgiant cells with necrotic sebocytes at the center of theinflammation were seen. A diagnosis of severegranulomatous dermatitis consistent with idiopathicsystemic granulomatous disease was made. No biopsyspecimens of other organs were obtained, so a diagnosis of systemic involvement could not be confirmed.

Treatment with oral prednisolone at 2 mg/kg/day wasinitiated. During a follow-up telephone conversation,the owner reported that the skin lesions and edema hadresolved after 2 weeks of therapy and that administrationof prednisolone was slowly tapered over another 2 weeksbefore being discontinued. Skin lesions had not recurred,and the patient’s attitude, appetite, and activity levelwere normal at follow-up 8 months after initialpresentation.

* * *The underlying trigger for idiopathic systemic

granulomatous disease in these cases is unknown. Thepatient in case one may have had a sequestered abscessthat resulted in sepsis after immunosuppression. Theabscess could have been an antigenic trigger, as could themeningioma or chronic liver disease. In the patient incase two, lesions developed after vaccination, leading to speculation regarding the role of vaccines in thepathogenesis of this disease. The horse was alsodiagnosed with herpesvirus infection and may have been a long-term carrier of the virus.

In the cases reported here, one horse did well after 4 weeks of oral administration of prednisolone with norecurrence of skin lesions at follow-up 8 months after initialpresentation. In the other case, apparent resolution ofgranulomatous disease occurred with oral administration of dexamethasone at 0.1 mg/kg/day, but adverse effects ofthe treatment may have resulted in the horse’s death.

H. Lateral thorax and rump after 17 days ofcorticosteroid treatment. I. Jugular furrow after 17 days of corticosteroid

treatment.

Experimental data support the concept that humansarcoidosis is an antigen-driven disorder in which Th1lymphocytes react excessively against an undeterminedself- or exogenous antigen.7 It has not been determinedwhether the cause is multifactorial or driven by a singleantigen.6 Tuberculosis and other mycobacterial diseaseshave been considered as the major cause of human sar-coidosis because of the similar histopathology of thetwo entities and the increased incidence of tuberculosisin some patients with sarcoidosis.6 A recent report8

demonstrated through polymerase chain reaction (PCR)assays that mycobacterial DNA is present in 80% ofcutaneous lesions of human sarcoidosis, although otherstudies9,10 have found no detectable mycobacterial DNAin multiple cases of lung and lymph node sarcoidosis. Aviral origin has also been suggested, with herpesvirus orhuman immunodeficiency virus being suggested as pos-sible causative agents.6

Too few cases of equine idiopathic systemic gran-ulomatous disease have been reported to allow validgenetic, infectious, or environmental associations to bemade. The disease may be more common in the west-ern United States, as are mycobacterial diseases in gen-eral.3 This has led to speculation that mycobacteria mayplay a role in the equine disease as well as in the humanequivalent. In a series of four cases,5 three horses hadpositive Borrelia spp titers, with Borrelia spp DNAidentified in one horse. The significance of this isunclear because the prevalence of positive Borrelia spptiters exceeds 20% of horses in endemic areas, and clin-ical illness associated with Borrelia burgdorferi infectionis uncommon in horses.11 In a recent retrospectivestudy12 of cutaneous equine sarcoidosis, PCR assays onparaffin-embedded specimens from eight horses werenegative for Mycobacteria spp, B. burgdorferi, Coccid-ioides immitis, Cryptococcus neoformans, and Corynebac-terium pseudotuberculosis.

Similar lesions have also been found in cattle withnaturally occurring and experimentally induced hairyvetch (Vicia sp) toxicosis. The disease in cattle may becaused by vetch resulting from hypersensitivity to one ormore plant constituents that induces the immunologicreaction.13 Similar generalized granulomatous diseasehas been found in horses that have ingested hairyvetch,14,15 but there has been no documented exposure tothe plant in most reports.

Because neither culturing nor electron microscopy hasrevealed viral, bacterial, or fungal organisms, it is likelythat idiopathic systemic granulomatous disease occurs

because of an abnormal host immune response to eitheran ingested or inhaled environmental antigen or anunderlying infectious or neoplastic process resulting inchronic antigenic stimulation.

TREATMENTResponse to therapy is not well documented because

of the small number of case reports in the literatureand the variable clinical course. The prognosis varieswith chronicity and severity of the disease. Adminis-tration of corticosteroids is the preferred treatment.Immunosuppressive doses of glucocorticoids may beeffective if administered early in the course of the dis-ease before the onset of wasting. Recommended drugsand doses include prednisolone at 2 to 4 mg/kg POq24h or dexamethasone at 0.2 to 0.4 mg/kg PO q24h.3

Prednisolone is preferred over prednisone in horses asshown in a recent study16 reporting reduced efficacy ofprednisone due to poor absorption and lack of produc-tion of the active metabolite prednisolone. Cortico-steroid therapy should be continued for several weeksto months with a slow taper when remission of clinicalsigns is achieved. There are a few reports2,3,17 of sponta-neous remission or successful treatment with pred-nisolone. In a recent retrospective study,12 three of ninehorses were euthanized soon after diagnosis, with theothers surviving as long as 12 years. Of the six thatsurvived, four had only cutaneous lesions, and the dis-ease resolved without specific treatment in the othertwo horses.

It appears that horses with only cutaneous involve-ment have a better long-term prognosis. In less severecases or cases that appear to regress, a single antigentrigger may no longer be present and/or the hostimmune response may be less reactive. Aggressiveimmunosuppression is probably warranted in mostcases. However, the relative benefits and risks of long-term corticosteroid therapy should be weighed in caseswith only cutaneous involvement because they mayresolve with more conservative management.

ACKNOWLEDGMENTThe authors thank Dr. Shelley Newman and Phil Snow for their assistance withthe photographs.

REFERENCES1. Sellers RS, Toribio RE, Blomme EA: Idiopathic systemic granulomatous dis-

ease and macrophage expression of PTHrP in a miniature pony. J CompPathol 125:214–218, 2001.

2. Scott DW: Equine Dermatology. St. Louis, WB Saunders, 2003, pp 675–680.

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Idiopathic Systemic Granulomatous Disease28 CE

1. A common name for equine idiopathic systemicgranulomatous disease isa. sarcoid.b. dermatophilosis.c. streptothricosis.d. sarcoidosis.

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ARTICLE #1 CE TESTThis article qualifies for 2 contact hours of continuingeducation credit from the Auburn University College ofVeterinary Medicine. Subscribers may purchase individualCE tests or sign up for our annual CE program.Those who wish to apply this credit to fulfill state relicensurerequirements should consult their respective stateauthorities regarding the applicability of this program.CE subscribers can take CE tests online and get real-time scores at CompendiumEquine.com.

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3. von Tscharner C, Kunkle G, Yager J (eds): Stannard’s illustrated equine der-matology notes: Immunologic diseases. Vet Dermatol 11(3):170–172, 2000.

4. Axon JE, Robinson P, Lucas J: Generalized granulomatous disease in a horse.Aust Vet J 82(1&2):48–51, 2004.

5. Rose JF, Littlewood JD, Smith K, et al: A series of four cases of generalizedgranulomatous disease in the horse, in Kwochka KW, Willemse T, vonTscharner C (eds): Advances in Veterinary Dermatology III. Boston, Butter-worth-Heinemann, 1998, pp 562–563.

6. English JC, Patel PJ, Greer KE: Sarcoidosis. J Am Acad Dermatol44(5):725–743, 2001.

7. Freedberg IM, Eisen AZ, Wolff K, et al: Fitzpatrick’s Dermatology in GeneralMedicine, ed 5. New York, McGraw-Hill, 1999, pp 1777–1783.

8. Li N, Bajoghli A, Kubba A, et al: Identification of mycobacterial DNA incutaneous lesions of sarcoidosis. J Cutan Pathol 26(6):271–278, 1999.

9. Vokura M, Lecossier D, du Bois RM, et al: Absence of DNA from mycobac-teria of the M. tuberculosis complex in sarcoidosis. Am J Respir Crit Care Med156:1000–1003, 1997.

10. Richter E, Greinert U, Kirsten D, et al: Assessment of mycobacterial DNA incells and tissues of mycobacterial and sarcoid lesions. Am J Respir Care Med153:375–380, 1996.

11. Fritz CL, Kjemtrupam AM: Lyme borreliosis. JAVMA 223(9):1261–1270,2003.

12. Spiegel IB, White SD, Foley JE, et al: A retrospective study of cutaneousequine sarcoidosis and its potential infectious aetiological agents. Vet Derma-tol 17(1):51–62, 2007.

13. Johnson B, Moore J, Woods LW, et al: Systemic granulomatous disease incattle in California associated with grazing hairy vetch (Vicia villosa). J VetDiagn Invest 4:360–362, 1992.

14. Anderson CA, Divers TJ: Systemic granulomatous inflammation in a horsegrazing hairy vetch. JAVMA 183(9):569–570, 1983.

15. Woods LW, Johnson B, Hietala SK, et al: Systemic granulomatous disease ina horse grazing pasture containing vetch (Vicia sp). J Vet Diagn Invest4:356–360, 1992.

16. Peroni DL, Stanley S, Kollias-Baker C, et al: Prednisone per os is likely tohave limited efficacy in horses. Equine Vet J 34(3):283–287, 2002.

17. Heath SE, Bell RJ, Clark EG, et al: Idiopathic granulomatous disease involv-ing the skin in a horse. JAVMA 197(10):1033–1036, 1990.

2. Diagnostic differential(s) for idiopathic systemicgranulomatous disease include(s)a. dermatophilosis.b. dermatophytosis.c. pemphigus foliaceus.d. all of the above

3. Biopsy specimens from the ________ can be easilyobtained and are the most valuable in the diagno-sis of idiopathic systemic granulomatous disease.a. lungsb. skinc. lymph nodesd. b and c

4. Skin biopsy specimens of horses with idiopathicsystemic granulomatous disease showa. lymphocytic–plasmacytic infiltrate.b. granulomatous inflammation with multinucleated giant

cells.c. nodular accumulations of neoplastic cells.d. intracellular bacteria.

5. The organ(s) most commonly involved in idio-pathic systemic granulomatous disease is(are) thea. skin.b. lungs.c. eyes.d. a and b

6. A diagnostic workup for idiopathic systemic gran-ulomatous disease might includea. a CBC and chemistry screen.b. thoracic radiography.c. abdominal ultrasonography.d. all of the above

7. Proposed causes of human sarcoidosis includea. infectious diseases such as tuberculosis.b. neoplasia.c. environmental pathogenesis with inorganic antigens as

the trigger.d. a and c

8. Theories regarding the pathogenesis of equineidiopathic systemic granulomatous diseaseincludea. mycobacterial infection.b. hairy vetch toxicosis.

c. herpesvirus.d. a and b

9. The preferred treatment of idiopathic systemicgranulomatous disease is administration of a. antibiotics.b. antifungals.c. corticosteroids.d. topical iodine.

10. The preferred oral corticosteroids in treatingidiopathic systemic granulomatous disease inhorses includea. prednisone.b. prednisolone.c. dexamethasone.d. b and c

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