Based on the results of the examinations and diagnostic tests, panuveitis, secondary glaucoma, retinal detachment, and retrobulbar
granuloma of both eyes secondary to systemic histoplasmosis were diagnosed.
TREATMENT AND PATIENT OUTCOME
Antifungal therapy with itraconazole was initiated at 5 mg/kg given orally twice a day, and the topical carbonic anhydrase
inhibitor dorzolamide was initiated three times a day to control the intraocular pressure in both eyes. Additionally, the
eyes were treated with the topical nonsteroidal anti-inflammatory diclofenac three times a day. The left eye was treated with
topical ciprofloxacin three times a day to prevent infection of the corneal ulcer. Clinical signs were found to gradually
improve over the following four weeks.
Unfortunately, owner compliance in this case was poor, and a relapse of clinical signs occurred after the owner discontinued
medical therapy several months later. On subsequent examination, the patient had developed right forelimb lameness and joint
effusion. Radiography of the forelimb showed lytic bony changes of the distal humerus and proximal radius and ulna. Histoplasma capsulatum organisms were identified by cytologic examination of aspirated joint fluid. Ultimately, because of the severity of changes
in the left eye, enucleation was recommended and performed by the referring veterinarian. Antifungal therapy was reinstituted,
and the patient continues to be monitored.
Histoplasmosis is a systemic mycotic infection caused by H. capsulatum, a dimorphic, saprophytic fungus that prefers nitrogen-rich soil and a humid environment.5,6 Geographic distribution is primarily reported for temperate and subtropical regions. In the United States, cases are most
commonly reported in regions of the Ohio, Missouri, and Mississippi river valleys.7-9 Histoplasmosis is often diagnosed between January and April, presumably because of the increased moisture in the soil during
this time.16 Although an uncommon disorder, histoplasmosis is the second most common fungal infection reported in cats.16
Typical histoplasmosis is the result of inhaling fungal spores (microconidia) that originate from the mycelial phase of the
fungus. At body temperature, these spores convert to yeast and are subsequently phagocytized by pulmonary macrophages.7,17 The organism undergoes intracellular replication in reticuloendothelial cells and may then become disseminated throughout
the body through lymphatic and hematogenous routes.9,18 This dissemination results in clinical disease that can affect the lungs, liver, spleen, choroid, lymph nodes, intestinal
mucosa, bone marrow, adrenal glands, bones, and skin, producing a variety of clinical signs.7,9
Clinical signs and ocular findings
In most cases, cats with the disseminated form of histoplasmosis have a nonspecific constellation of signs including weight
loss, weakness, dehydration, depression, fever, anorexia, and anemia.16,18-21 The incidence of respiratory signs (dyspnea, tachypnea, coughing) ranges from 39% to 45%.16,20
Ocular abnormalities were reported in 24% of cases in one study.16 The most common ocular abnormalities in patients with disseminated histoplasmosis included granulomatous chorioretinitis,
anterior uveitis, and retinal detachment.6,9 In one retrospective study in which 20 cats with histoplasmosis received an ophthalmic examination, retinal detachments
were noted in 25%.20 Granulomatous blepharitis and optic neuritis have also been reported.17,19 To our knowledge, this case is the first with bilateral retrobulbar granulomas secondary to systemic histoplasmosis.
Diagnosing this condition can be challenging since serologic tests for H. capsulatum antigen often yield false negative results in patients with active disease.7,19 Thus, identification of the organism on cytologic preparations is the most likely way to obtain a rapid definitive diagnosis.5
Although ocular aspiration was not performed in this case to confirm the organisms within the eye, it has been reported that
in cats with systemic mycoses, intraocular inflammation is caused by the organism within the eye and not as a result of a
systemic inflammatory response.9
Recently, urine antigen testing (MVista—MiraVista Diagnostics) has become an important tool in the diagnosis of histoplasmosis.
The sensitivity of this test has been reported as 94% for the detection of antigen in the urine of affected cats.22
The highest reported success rate for the treatment of histoplasmosis has been with itraconazole (5 mg/kg orally twice a day).21,23 However, the administration of a combination of amphotericin B and ketoconazole has also been successful.19 Systemic antifungal agents should be administered until clinical signs resolve. Protracted therapy is often required.
Monitoring serial antigen concentrations will help you evaluate a patient's response to therapy and determine for how long
the therapy should be continued.24 In one study, only 55% of cats survived to discharge; the median duration of treatment for these cats was five months.20
It can be difficult to clear infectious organisms from within the eye, and the eye may serve as a future nidus of infection
even after protracted systemic antifungal therapy. Cases with ocular involvement are considered to have disseminated disease,
which is associated with a poor-to-guarded prognosis.
Nonspecific therapy for secondary ocular signs is also necessary. Topical anti-inflammatory agents are aggressively given
to reduce anterior uveitis. Topical corticosteroids (1% prednisolone acetate, 0.1% dexamethasone) may be administered in cats
without corneal ulceration. For cats with corneal ulceration, administering a topical nonsteroidal anti-inflammatory agent,
such as 0.03% flurbiprofen or 0.1% diclofenac, until the corneal ulcer is resolved is recommended. Topical anti-inflammatory
agents are not effective for treating posterior uveitis, so when not contraindicated, a systemic anti-inflammatory agent should
also be administered.
Administering a topical cycloplegic (e.g. 1% atropine) is also recommended to reduce ocular pain and the incidence of posterior synechiae; however, this drug is contraindicated
in patients with secondary glaucoma. In this case, intraocular pressure values were elevated in the left eye and within established
reference ranges in the right eye.25 However, given the degree of uveitis seen on examination, intraocular pressure values were considered inappropriate, and
therapy with a topical carbonic anhydrase inhibitor (2% dorzolamide) was instituted three times daily in both eyes.