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Basics ⬇

Basics

Definition

A systemic fungal infection caused by Histoplasma capsulatum.

Pathophysiology

  • Soil-borne dimorphic fungus with the mycelial form growing best in bird manure or organically enriched soil.
  • Mycelium in the soil-produces infectious spores (microconidia); inhaled into the terminal airways.
  • Spores-germinate in the lungs; develop into yeast form that reproduce by budding.
  • Yeast are phagocytized by mononuclear phagocytes.
  • Mononuclear phagocytes-distribute the organisms throughout the body.
  • Ingested organisms may directly infect the intestinal tract.
  • Immune response-determines whether disease develops; affected animals often develop transient, asymptomatic infection.

Systems Affected

  • Cats-respiratory tract main site of infection; bone, bone marrow, liver, spleen, skin, and lymph nodes also affected; intestinal tract, eyes, kidneys, adrenals, and brain less frequently involved.
  • Dogs-intestinal tract most frequently involved site; liver, lung, spleen, and lymph nodes often involved; bones, bone marrow, kidneys, adrenals, oral cavity, tongue, eyes, and testes less frequently affected.

Genetics

N/A

Incidence/Prevalence

Prevalence of clinically relevant histoplasmosis relatively low in cats and dogs; an active practice, even in endemic areas, would see three to four cases a year.

Geographic Distribution

  • Endemic areas-Ohio, Missouri, Mississippi, Tennessee, and St. Lawrence river basins.
  • Also seen in Texas, the southeastern United States, the Great Lakes region, and California.
  • Has been isolated from the soil of 31 continental US states.

Signalment

Species

Dog and cat

Breed Predilections

N/A

Mean Age and Range

  • Cats-predominantly young; many <1 year of age; all ages can be infected.
  • Dogs-most often young to middle-aged; all ages can be infected.

Predominant Sex

  • Cats-females may be overrepresented.
  • Dogs-none reported.

Signs

Historical Findings

Cat

  • Insidious onset over days to weeks.
  • Anorexia, weight loss, and dyspnea-most common.
  • Coughing occasionally.
  • Lameness.
  • Ocular discharge.
  • Diarrhea.

Dogs

  • Weight loss, depression, and diarrhea with straining-most common.
  • Coughing.
  • Dyspnea.
  • Exercise intolerance.
  • Lymphadenopathy.
  • Lameness and eye and skin changes-less common.

Physical Examination Findings

Cats

  • Fever to 40°C (104°F).
  • Increased respiratory effort and harsh lung sounds.
  • Mucous membranes pale.
  • Enlarged lymph nodes.
  • Lameness, ocular changes, and skin lesions may be found.

Dogs

  • Thin to emaciated.
  • Fever to 40°C (104°F).
  • Hepatosplenomegaly.
  • Mucous membranes often pale.
  • Icterus and ascites occasionally seen.
  • Coughing and dyspnea associated with harsh lung sounds.
  • Ocular and skin lesions less commonly noted.

Cause

H. capsulatum

Risk Factors

  • Bird roosts where the soil is enriched with bird or bat droppings are high-risk environments; old chicken coops and caves have been implicated.
  • Exposure to airborne dust contaminated with fungal spores coming from sites of fungal growth (especially indoor cats).
  • Tissue samples from nearly half of stray dogs and cats from an endemic area were positive for Histoplasma, supporting the theory that many people and animals are infected but few develop clinically significant disease.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

Cats

  • Dyspnea from fungal pneumonia-differentiate from heart failure, feline asthma, lymphoma, pneumonia, pleural effusion, and other fungal pneumonias.
  • Lameness-differentiate from trauma.
  • Ocular changes-differentiate from lymphoma, toxoplasmosis, and feline infectious peritonitis.

Dogs

  • Severe chronic diarrhea and weight loss-consider lymphocytic plasmacytic enteritis, eosinophilic enteritis, lymphoma, chronic parasitism, and pancreatic exocrine insufficiency.
  • Diarrhea and anemia-consider severe inflammatory bowel disease, lymphoma or other intestinal neoplasia, and parasitism (hookworm infection).
  • Hepatosplenomegaly and peripheral lymphadenopathy-consistent with lymphoma.
  • Respiratory signs-differentiate from infectious causes (distemper, bacterial, or other fungal pneumonia), chronic bronchitis, pleural effusion, heart failure, and pulmonary hypertension.

CBC/Biochemistry/Urinalysis

  • Moderate to severe nonregenerative anemia common.
  • Leukocyte counts-usually normal; some patients have a leukocytosis; patients with bone marrow involvement may be leukopenic.
  • Histoplasma organisms-may be found in circulating neutrophils and monocytes; 2–4 µm round body with a basophilic center and lighter halo.
  • Severe liver involvement-may see hyperbilirubinemia and high ALT activity.
  • Dogs with severe intestinal histoplasmosis often have low total protein and exhibit panhypoproteinemia.

Other Laboratory Tests

  • AGID test-for antibodies; supports diagnosis; positive results indicate active disease; previous infections may produce false-positive results; many animals with active disease are negative on serology.
  • Antigen testing-antigen excretion in urine may provide a more accurate assay for identifying infected animals, although little data available; has been found to be a sensitive assay in cats; resource: www.miravistalabs.com.
  • Coombs' test-may be positive because antibodies to Histoplasma may cross-react with RBCs; steroid therapy contraindicated.

Imaging

Thoracic Radiography

  • Dogs-diffuse interstitial to nodular pneumonia; enlarged tracheobronchial lymph nodes compressing the tracheal bifurcation; old lung lesions may be calcified, coin-like opacities that suggest metastatic tumors.
  • Cats-usually a diffuse interstitial pattern of lung involvement; calcification and tracheobronchial lymphadenopathy uncommon.

Abdominal and Bone Radiography

  • Dogs-hepatosplenomegaly, mesenteric lymphadenopathy, and potentially ascites..
  • Cats and less often dogs-bone lesions predominantly osteolytic and usually occur distal to the elbows and stifles.

Diagnostic Procedures

  • Identification of organisms on cytology, histopathology, or culture-definitive.
  • Tissue samples-enlarged lymph nodes, liver, and spleen are higher yield sites; rectal scrapings may be rich in organisms; bone marrow; lung aspirates (when less invasive procedures are not diagnostic); tracheal washes inconsistent.
  • Urine antigen assay has high sensitivity in initial report.

Pathologic Findings

  • Multifocal, granulomatous lesions in organs rich in reticuloendothelial cells (e.g., spleen, liver, lymph nodes, lungs, and bone marrow).
  • Dogs-gut prime site of involvement; tracheobronchial lymph node enlargement common.
  • Cats-predominantly respiratory involvement.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Usually outpatient with oral itraconazole.
  • Inpatient with intravenous amphotericin B-dogs with severe intestinal disease and malabsorption.

Nursing Care

  • Dogs on amphotericin B therapy-keep well hydrated to decrease potential for nephrotoxicity.
  • Emaciated animals with malabsorption-consider total parenteral nutrition until the intestinal disease is resolved enough for adequate food absorption.
  • Animals with severe dyspnea-oxygen supplementation.

Activity

Dogs with dyspnea-reduce.

Diet

Good-quality, easily absorbed, palatable food.

Client Education

  • Discuss possible areas of exposure in the home environment.
  • Inform client that both pets and family members may have been exposed to the same source but that the animal is not a hazard to the family.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Itraconazole

  • Drug of choice if adequate intestinal function for drug absorption exists.
  • Dogs and cats-5 mg/kg PO q12h; give with a high-fat meal.
  • Be cautious about compounded itraconazole because absorption may not be acceptable.
  • Duration depends on the clinical response; minimum treatment is 90 days.

Intravenous Amphotericin B

Dogs

  • With severe inflammatory bowel disease and malabsorption-use until patient begins to gain weight; then start on itraconazole.

  • Patient must be well hydrated before starting treatment; do not give amphotericin B in electrolyte solutions that may precipitate the drug.
  • Usual dose-0.5–1.0 mg/kg IV q48h.
  • Reconstitute in 5% dextrose and dilute for administration.
  • Normal renal function-dilute in 60–120 mL 5% dextrose and give over 2 hours.
  • Some renal compromise-dilute in 0.5–1 L 5% dextrose and give over 3–4 hours to reduce renal toxicity.

Cats

  • Use cautiously.
  • Usual dose-0.25 mg/kg IV in 5% dextrose over 3–4 hours q48h.
  • More sensitive to the drug than are dogs.

Fluconazole

  • Eye and CNS involvement may best be treated with fluconazole that penetrates the blood-brain barrier.
  • Use for dogs that cannot be given amphotericin B.
  • Usual dose (intravenous form)-5 mg/kg IV q12h until intestinal absorption allows oral itraconazole treatment.

Contraindications

Amphotericin B-caution with azotemic patients (in life-threatening situation, may still consider its use); monitor creatinine throughout therapy-elevation above normal or 20% greater than baseline is considered significant.

Precautions

  • Steroids-use with caution; allows proliferation of Histoplasma; life-threatening respiratory distress due to infiltrative lung disease or hilar lymphadenopathy justifies use of dexamethasone 0.1–0.2 mg/kg IV daily for 2–3 days.
  • Itraconazole and fluconazole-hepatic toxicity; temporarily discontinue if patient becomes anorexic or if serum ALT activity >300 U/L; restart at half-dose after appetite improves.

Possible Interactions

Itraconazole-inhibits cytochrome P450 system (CYP3A) and can increase concentrations of cyclosporine, digoxin, and midazolam in humans.

Alternative Drug(s)

None

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Serum ALT-with itraconazole treatment; check monthly or if the patient becomes anorexic.
  • Chest radiographs-with pulmonary involvement; check after 60 days of treatment to assess improvement; repeat at 30-day intervals and stop treatment when infiltrates are clear or remaining lung lesions fail to improve, indicating residual scarring; may be difficult to differentiate between residual fibrotic lesions and active disease; continue treatment for at least 1 month after all signs of active disease have resolved.
  • Monitoring urinary antigen levels may be helpful.

Prevention/Avoidance

  • Avoid suspected areas of exposure (e.g., bird roosts).
  • Recovered dogs are potentially immune.

Possible Complications

Recurrence possible; requires a second course of treatment.

Expected Course and Prognosis

  • Treatment-duration is usually about 4 months; drugs are expensive, especially for large dogs.
  • Prognosis-good for stable patients without severe dyspnea; influenced by severity of lung involvement and debility of patient.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

No apparent predisposing conditions.

Age-Related Factors

N/A

Zoonotic Potential

  • Yeast form is not spread from animals to humans.
  • Care must be taken to avoid needlestick injury when collecting aspirates.
  • Infection can occur from cuts when doing necropsies on infected animals.

Pregnancy/Fertility/Breeding

Itraconazole-no teratogenic effects in rats and mice at therapeutic doses; embryotoxicity found at high doses; no dog or cat studies; however, azole drugs can be teratogenic, use with caution in pregnant animals.

Abbreviations

  • AGID = agar gel immunodiffusion
  • ALT = alanine transaminase
  • RBC = red blood cell

Author Daniel S. Foy

Consulting Editor Stephen C. Barr

Acknowledgment The author and editors acknowledge the prior contribution of Alfred M. Legendre.

Client Education Handout Available Online

Suggested Reading

Cook AK, Cunningham LY, Cowell AK, et al. Clinical evaluation of urine Histoplasma capsulatum antigen measurement in cats with suspected disseminated histoplasmosis. J Feline Med Surg 2012, 14:512–515.

Brömel C, Greene CE. Histoplasmosis. In: Greene CE, ed., Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Saunders Elsevier, 2012, pp. 614–621.

Lin Blache J, Ryan K, Arceneaux K. Histoplasmosis. Compend Contin Educ Vet 2011, 33:E1–E10.

Schulman RL, McKiernan BC, Schaeffer DJ. Use of corticosteroids for treating dogs with airway obstruction secondary to hilar lymphadenopathy caused by chronic histoplasmosis: 16 cases (1979–1997). J Am Vet Med Assoc 1999, 214:1345–1448.