Histoplasmosis

Histoplasmosis is a systemic fungal infection caused by the dimorphic fungus Histoplasma capsulatum, an organism found in soil contaminated with bird or bat droppings in endemic geographic regions. This disease is one of the most common systemic mycoses affecting dogs in certain areas of North America, particularly the Ohio, Mississippi, and Missouri River valleys where environmental conditions favor fungal growth. Dogs become infected by inhaling fungal spores from contaminated soil, and the infection can range from mild, self-limiting respiratory disease to severe, life-threatening disseminated illness affecting multiple organ systems.

The pathophysiology of histoplasmosis involves a temperature-dependent transformation of the fungus. In the environment, Histoplasma exists as a mold that produces infectious spores called microconidia. When these spores are inhaled and enter the warm environment of the mammalian body, they convert to a yeast form capable of surviving and replicating within macrophages, the immune cells that normally engulf and destroy pathogens. This ability to parasitize the very cells meant to eliminate it makes Histoplasma a particularly successful intracellular pathogen. From the lungs, the infection can spread through the bloodstream and lymphatic system to virtually any organ in the body.

The clinical impact of histoplasmosis on affected dogs varies considerably based on the immune response, infectious dose, and whether the disease remains localized or becomes disseminated. Many dogs exposed to Histoplasma develop subclinical infections that resolve without ever causing noticeable illness. However, when clinical disease develops, it can be debilitating and potentially fatal without treatment. The gastrointestinal tract is commonly affected in dogs, unlike in some other species, leading to chronic diarrhea, weight loss, and malabsorption. Pulmonary involvement causes respiratory signs, while disseminated disease can affect the liver, spleen, bone marrow, lymph nodes, eyes, skin, and other organs.

With appropriate antifungal treatment, many dogs with histoplasmosis can achieve remission or cure, though therapy typically requires months of medication. Early diagnosis significantly improves outcomes, as advanced or disseminated disease is more challenging to treat successfully. The prognosis depends heavily on the extent of organ involvement and the dog's overall condition at diagnosis. Veterinary care is essential for accurate diagnosis, appropriate treatment selection, and monitoring of response to therapy. Without treatment, severe histoplasmosis typically progresses and can be fatal.

The primary cause of histoplasmosis in dogs is infection with Histoplasma capsulatum, a dimorphic fungus endemic to specific geographic regions worldwide. In North America, the organism is concentrated in the Ohio, Mississippi, and Missouri River valleys, as well as parts of the southeastern United States. The fungus thrives in nitrogen-rich soil contaminated with bird or bat droppings, with particularly high concentrations found in areas where birds roost, chicken houses, bat caves, and sites with accumulated guano. Dogs become infected by inhaling airborne microconidia, the infectious spore form produced by the environmental mold phase of the fungus.

Genetic and hereditary factors do not directly cause histoplasmosis, as this is an acquired infectious disease. However, individual variations in immune function influence susceptibility to clinical disease following exposure. Many dogs inhale Histoplasma spores in endemic areas without developing clinical illness, while others progress to symptomatic disease. This variation likely reflects differences in innate and adaptive immune responses. Cell-mediated immunity, particularly T-lymphocyte function, is crucial for controlling Histoplasma infection. No specific genetic mutations have been identified that predispose dogs to histoplasmosis, but individual immune competence plays a significant role in disease expression.

Environmental and lifestyle factors are critical determinants of histoplasmosis risk. Dogs living in or traveling to endemic regions face the highest exposure risk. Specific activities that increase exposure include digging in contaminated soil, exploring old buildings or barns with bird infestations, investigating bat caves or roosting sites, and spending time in areas where soil has been recently disturbed. Construction activities, demolition, and excavation in endemic areas can aerosolize large numbers of spores, creating conditions for multiple exposures. Hunting dogs and outdoor dogs in endemic regions may have higher exposure rates than indoor dogs.

Several risk factors increase a dog's susceptibility to developing clinical histoplasmosis. Young dogs, particularly those under four years of age, are diagnosed more frequently than older dogs, possibly reflecting both exposure patterns and immune maturity. Immunocompromised dogs, including those receiving immunosuppressive medications or those with underlying diseases affecting immune function, face elevated risk for severe disease. Dogs receiving high-dose corticosteroids are particularly vulnerable. Large infectious doses from heavy environmental contamination may overwhelm even healthy immune systems. Season may influence exposure, with soil disturbance during dry conditions potentially releasing more spores.

The mechanism of disease development begins with inhalation of microconidia into the lower respiratory tract. In the warm lung environment, the fungus transforms to its yeast phase. Macrophages phagocytose the yeasts, but Histoplasma has evolved mechanisms to survive and replicate within these cells rather than being destroyed. The infected macrophages can disseminate through the lymphatic system and bloodstream, carrying the infection to other organs. The body's cell-mediated immune response is critical for controlling the infection. In immunocompetent individuals, granulomatous inflammation typically contains the organism, potentially leading to resolution or latency. In susceptible individuals, progressive primary infection or reactivation of latent infection can result in clinical disease.

Early warning signs of histoplasmosis in dogs may be nonspecific and subtle, making early recognition challenging. Initial symptoms often include mild lethargy, slightly decreased appetite, and low-grade fever that may fluctuate. Some dogs develop a soft cough or mild respiratory signs that may be attributed to other common causes. Subtle weight loss may occur before more obvious clinical signs develop. Because these early signs mimic many other conditions, histoplasmosis often is not suspected initially, particularly in dogs without known exposure to endemic areas. The insidious onset and gradual progression can delay diagnosis for weeks to months.

Common symptoms of histoplasmosis vary depending on which organ systems are primarily affected. Gastrointestinal involvement is particularly common in dogs and presents with chronic large bowel diarrhea, often containing mucus or fresh blood. Affected dogs may strain to defecate and have increased frequency of bowel movements. Weight loss is common and can be profound despite maintained or only mildly decreased appetite, reflecting malabsorption from intestinal disease. Respiratory signs including cough, increased respiratory rate, and exercise intolerance occur with pulmonary involvement. Dogs with disseminated disease may show combinations of respiratory and gastrointestinal signs along with systemic illness.

Behavioral changes in dogs with histoplasmosis primarily relate to the systemic effects of chronic infection. Progressive lethargy and decreased interest in normal activities are common. Affected dogs may become withdrawn, sleep more than usual, and show reduced enthusiasm for play, walks, or interaction. Depression is frequently noted as the disease progresses. Dogs may show changes in eating behavior, including reluctance to eat, pickiness, or complete anorexia in advanced cases. Discomfort from abdominal involvement may cause restlessness or reluctance to lie in certain positions.

Physical signs visible to owners include progressive weight loss that may become severe, creating a visibly thin or emaciated appearance. The coat may become dull and unkempt. Pale gums may indicate anemia, which commonly accompanies disseminated disease. Enlarged lymph nodes may be palpable, particularly under the jaw or in front of the shoulders. Some dogs develop eye abnormalities including redness, cloudiness, or visible changes to eye structures when ocular histoplasmosis occurs. Skin lesions, though less common in dogs than some other systemic mycoses, may appear as nodules, draining tracts, or ulcerations. Abdominal distension from organ enlargement or fluid accumulation may be evident.

Symptom progression in histoplasmosis typically follows a chronic, gradually worsening course over weeks to months. Weight loss becomes increasingly pronounced, and dogs may lose significant body condition. Diarrhea may worsen or fluctuate in severity. Dogs with pulmonary involvement may develop progressive respiratory difficulty. Fever may become more persistent or higher. Without treatment, affected dogs generally deteriorate progressively, developing signs of multiple organ involvement. Bone marrow suppression can lead to worsening anemia and increased susceptibility to secondary infections. The rate of progression varies but is generally faster in young dogs and those with heavily disseminated disease.

Emergency symptoms requiring immediate veterinary attention include severe respiratory distress, collapse, extreme weakness, bloody diarrhea with significant blood loss, signs of internal bleeding such as pale gums and weakness, or acute deterioration in a dog being treated for histoplasmosis. High fever with signs of systemic illness such as complete anorexia and severe depression warrants urgent evaluation. Dogs showing signs of shock, including weak pulse, cold extremities, and altered consciousness, need emergency care. Sudden blindness or painful eye changes suggest ocular involvement requiring prompt attention.

The initial veterinary examination for suspected histoplasmosis involves a comprehensive physical assessment and detailed history. The veterinarian will evaluate body condition, examine the abdomen for organomegaly or discomfort, auscultate the chest for respiratory abnormalities, assess lymph nodes for enlargement, and examine the eyes for signs of fungal involvement. Travel history and geographic location are crucial information, as histoplasmosis diagnosis requires consideration of exposure to endemic areas. Questions about the duration and progression of symptoms, living environment, and activities help establish the clinical picture. Based on findings, specific diagnostic tests will be recommended.

Diagnostic tests for histoplasmosis include various methods to identify the organism or the body's response to infection. Cytology of rectal scrapings, lymph node aspirates, bone marrow aspirates, or other affected tissues may reveal the characteristic small intracellular yeasts within macrophages. This direct visualization provides rapid presumptive diagnosis. Histopathology of tissue biopsies with special staining can confirm the presence of organisms. Urine and serum antigen tests detect Histoplasma galactomannan antigen and offer non-invasive diagnostic options with good sensitivity for disseminated disease. Serology testing for antibodies can support diagnosis but may be negative early in infection or in immunocompromised dogs. Fungal culture is definitive but slow, requiring two to four weeks, and presents laboratory safety concerns due to the infectious nature of the mold form. Thoracic radiographs evaluate pulmonary involvement, and abdominal ultrasound assesses liver, spleen, and lymph node changes.

Differential diagnoses that must be distinguished from histoplasmosis include other systemic fungal infections such as blastomycosis, coccidioidomycosis, and cryptococcosis, which can produce similar clinical presentations. Inflammatory bowel disease and other chronic enteropathies must be considered for dogs presenting with chronic diarrhea and weight loss. Gastrointestinal lymphoma and other intestinal neoplasia can mimic the GI presentation of histoplasmosis. For dogs with respiratory signs, bacterial pneumonia, other fungal pneumonias, and pulmonary neoplasia are differentials. Systemic diseases causing weight loss, lymphadenopathy, and organomegaly, including lymphoma and other cancers, require differentiation through diagnostic testing.

Diagnosis confirmation typically relies on a combination of compatible clinical signs, supportive diagnostic imaging, and definitive identification of the organism through cytology, histopathology, or positive antigen testing. Positive urine or serum antigen testing combined with appropriate clinical presentation and geographic exposure provides strong evidence for diagnosis. Cytologic demonstration of the characteristic yeasts within macrophages is definitive when organisms are visualized. Once diagnosis is confirmed, the extent of disease involvement is assessed through comprehensive testing including complete blood count to evaluate for anemia and bone marrow suppression, serum chemistry to assess liver and kidney function, and imaging studies as indicated.

Initial treatment for histoplasmosis in dogs focuses on beginning appropriate systemic antifungal therapy promptly upon diagnosis. Unlike some acute infections, histoplasmosis treatment does not typically require emergency stabilization procedures in most cases. However, dogs presenting in poor condition may need supportive care including intravenous fluids for dehydration, nutritional support for malnourished patients, and treatment of secondary complications. Blood transfusions may be necessary for severely anemic dogs. The cornerstone of treatment is long-term oral antifungal medication, which is typically initiated immediately upon confirmed or strongly suspected diagnosis.

Medical management of histoplasmosis relies primarily on itraconazole, which is considered the treatment of choice for most canine cases. This azole antifungal achieves good tissue concentrations and has proven efficacy against Histoplasma. Treatment with itraconazole typically continues for a minimum of four to six months, with many dogs requiring longer courses. Fluconazole is an alternative azole antifungal that may be used, particularly when central nervous system or ocular involvement is present due to better penetration into these tissues. Amphotericin B, administered intravenously, may be used for initial treatment of severely ill dogs or those not responding to azole therapy, though its nephrotoxicity requires careful monitoring and administration protocols. Treatment duration is guided by clinical response and resolution of urine antigen positivity.

Surgical intervention plays a limited role in histoplasmosis treatment. Surgical biopsy of affected tissues may be needed for definitive diagnosis in some cases. Rarely, surgical intervention might be considered for localized granulomatous lesions not responding to medical therapy or causing significant obstruction. However, antifungal medication remains essential, and surgery alone cannot cure systemic fungal infection. The vast majority of histoplasmosis cases are managed medically without surgical intervention.

Supportive care is often crucial, particularly for dogs presenting with advanced disease. Nutritional support through highly digestible, calorie-dense diets helps address weight loss and malnutrition. Dogs with severe gastrointestinal involvement may benefit from easily digestible foods, and some require appetite stimulants or temporary feeding tubes. Management of anemia may include iron supplementation for regenerative anemia or blood transfusions for severe cases. Anti-diarrheal medications and probiotics may provide symptomatic relief for dogs with persistent diarrhea. Pain management is provided as needed. Treatment of any secondary bacterial infections with appropriate antibiotics supports recovery.

Alternative and complementary therapies for histoplasmosis are limited, and no herbal or alternative treatments have demonstrated efficacy against this fungal infection. Supportive measures including optimal nutrition, stress reduction, and management of concurrent conditions may benefit the dog's overall recovery. Some veterinarians recommend probiotics to support gastrointestinal health, particularly during treatment of GI histoplasmosis. However, owners should understand that antifungal medication is essential and cannot be replaced by alternative therapies. Failure to complete appropriate antifungal treatment results in disease progression.

Treatment decisions are influenced by multiple factors including the extent of disease, organ systems involved, the dog's overall condition, and practical considerations. Dogs with mild, localized disease generally respond well to standard oral antifungal therapy. Severe or disseminated disease may require initial intensive treatment followed by prolonged maintenance therapy. The dog's ability to tolerate oral medications and the owner's ability to comply with long-term treatment affect outcomes. Cost is a significant consideration, as months of antifungal therapy with regular monitoring is expensive. Urine antigen testing provides objective monitoring of treatment response, with declining titers indicating efficacy. Expected outcomes with appropriate treatment are generally favorable for dogs that respond to initial therapy, though severely debilitated patients carry a more guarded prognosis.

Recovery from histoplasmosis is typically a gradual process extending over months of treatment. Clinical improvement often becomes apparent within the first two to four weeks of therapy, with increased energy, improved appetite, and stabilization or reversal of weight loss. Diarrhea typically improves within the first few weeks, though complete resolution may take longer. Respiratory signs gradually improve in dogs with pulmonary involvement. However, clinical improvement alone does not indicate complete resolution, and treatment must continue for the full prescribed duration. Most dogs require a minimum of four to six months of antifungal therapy, with some needing longer courses depending on disease extent and response.

Post-treatment care involves continued antifungal medication as prescribed, with regular veterinary monitoring to assess treatment response. Urine antigen testing is valuable for objective monitoring, with declining or negative results indicating treatment success. Serial antigen testing is typically performed every one to three months during treatment. Complete blood counts and serum chemistry panels monitor for drug-related side effects and assess improvement in any disease-related abnormalities. Treatment generally continues until urine antigen is negative and clinical signs have resolved, followed by additional therapy to reduce relapse risk. After treatment completion, periodic monitoring for several months helps detect any recurrence early.

Prognosis for canine histoplasmosis varies based on disease extent, organ systems involved, and the dog's condition at diagnosis. Dogs with localized pulmonary disease generally have good prognosis with appropriate treatment. Gastrointestinal histoplasmosis can often be successfully treated, though dogs with severe malabsorption and emaciation at diagnosis face more challenging recoveries. Disseminated disease carries a more guarded prognosis, particularly when bone marrow involvement has caused significant cytopenias. Factors associated with poorer outcomes include severe anemia, marked hypoalbuminemia, very low body weight, and involvement of multiple organ systems. Overall, survival rates with treatment typically range from sixty to ninety percent depending on disease severity.

The long-term outlook for dogs successfully treated for histoplasmosis is generally positive. Dogs achieving negative antigen status and clinical resolution can return to normal or near-normal lives. Unlike some infections, histoplasmosis typically does not cause permanent organ damage in successfully treated cases, allowing full recovery of function. Relapse can occur, particularly if treatment is discontinued prematurely, making completion of the full prescribed course essential. Dogs residing in endemic areas face ongoing exposure risk and could potentially become reinfected, though prior infection may provide some degree of immunity. Regular veterinary care and owner vigilance for recurrent signs support early detection of any relapse.

Primary prevention of histoplasmosis focuses on reducing exposure to Histoplasma capsulatum spores in endemic areas. Completely avoiding exposure is impractical for dogs living in endemic regions, but certain measures can reduce risk. Avoiding areas known to be heavily contaminated, such as old chicken houses, bat caves, areas with large bird roosts, and sites where soil has been recently disturbed, limits exposure to high concentrations of spores. Keeping dogs away from construction or demolition sites in endemic areas during active soil disturbance reduces inhalation risk. Dogs should not be allowed to dig extensively in potentially contaminated soil. Indoor housing during high-risk activities such as nearby excavation can provide some protection.

Breeding and genetic considerations for histoplasmosis prevention are minimal since this is an acquired infectious disease without hereditary components. No specific breeding recommendations exist for histoplasmosis prevention. However, breeding dogs in highly endemic areas should be maintained in good health with minimal exposure to high-risk environments. Pregnant or nursing dogs are not specifically more susceptible, but maintaining their overall health supports immune function. Dogs with immunocompromising conditions requiring immunosuppressive therapy may not be ideal breeding candidates due to overall health concerns rather than histoplasmosis specifically.

Nutritional factors supporting histoplasmosis resistance center on maintaining a healthy immune system through optimal nutrition. A complete, balanced diet providing all essential nutrients supports immune function and disease resistance. Maintaining healthy body weight avoids the immune impairment associated with both obesity and malnutrition. While no specific supplements have proven preventive against histoplasmosis, overall good nutrition is one component of the body's ability to resist infections. Adequate protein intake supports immune cell production and function.

Health maintenance practices supporting histoplasmosis prevention include regular veterinary care, prompt treatment of any conditions affecting immune function, and minimizing use of immunosuppressive medications when medically appropriate. Dogs requiring immunosuppressive therapy for conditions like immune-mediated diseases should be monitored closely for signs of opportunistic infections. Avoiding unnecessary stress, which can impair immune function, benefits overall health. Regular preventive care including parasite control, vaccination against other diseases, and dental care maintains the dog's health reserve.

Early intervention when histoplasmosis is suspected is critical for optimal outcomes. Dogs in endemic areas presenting with chronic respiratory signs, unexplained weight loss, chronic diarrhea, or nonspecific illness should be evaluated for fungal infection. A travel history including visits to endemic regions should prompt consideration of histoplasmosis in dogs presenting with compatible signs. Early diagnosis and treatment, before severe debilitation occurs, is associated with better outcomes. Owners of dogs in endemic areas should be aware of the condition and its signs, facilitating prompt veterinary consultation when problems are noticed.

Daily management of a dog with histoplasmosis during treatment centers on consistent medication administration and supportive care. Itraconazole is typically administered once or twice daily with food to enhance absorption, making meal times convenient dosing opportunities. Owners should establish a reliable medication routine and use reminders if needed to ensure doses are not missed. Monitoring food intake, water consumption, energy level, body weight, and stool quality provides ongoing assessment of treatment response. Dogs recovering from significant weight loss benefit from frequent, calorie-dense meals. A simple log of daily observations can help track progress and provide useful information for veterinary visits.

Home environment modifications for dogs with histoplasmosis primarily focus on providing comfort and supporting recovery. A quiet, comfortable resting area allows dogs to conserve energy during recovery. Dogs with respiratory involvement benefit from avoiding dusty environments and maintaining good air quality. Easy access to food, water, and elimination areas reduces energy expenditure for debilitated dogs. Dogs that have lost significant muscle mass may benefit from padded bedding to prevent pressure sores. Climate control maintaining comfortable temperatures supports overall well-being during recovery.

Maintaining quality of life during histoplasmosis treatment involves balancing rest with appropriate activity as the dog's condition allows. Dogs feeling better as treatment progresses should be allowed gentle exercise and activities they enjoy, as this supports mental health and muscle maintenance. However, strenuous activity should be avoided until recovery is well established. Mental stimulation through calm interaction, gentle play, and companionship prevents boredom during convalescence. Maintaining normal routines as much as possible provides psychological comfort. Dogs with advanced disease may have very limited energy, and their activity level should be guided by their capabilities.

Ongoing monitoring during treatment includes watching for signs of improvement as well as potential treatment complications. Positive signs include weight gain, improved appetite, resolution of diarrhea, decreased respiratory effort, and increased energy and activity. Warning signs requiring veterinary contact include vomiting or loss of appetite that could indicate medication intolerance, jaundice or dark urine suggesting liver problems, worsening of any clinical signs despite treatment, or development of new symptoms. Dogs receiving azole antifungals require periodic liver enzyme monitoring. Regular veterinary rechecks allow assessment of treatment response and adjustment of therapy as needed.

Caregiver support is important given the long duration and cost of histoplasmosis treatment. Owners should be prepared for a treatment commitment of several months, with associated medication costs, monitoring expenses, and frequent veterinary visits initially. Understanding the expected timeline and having realistic expectations about gradual improvement helps prevent discouragement. Financial planning, including discussion of costs upfront and exploration of payment options, prevents treatment interruption due to financial constraints. Emotional support from family, friends, or online communities helps caregivers cope with the stress of managing a seriously ill pet. Open communication with the veterinary team about concerns and challenges ensures the best possible care within the owner's capabilities.

Histoplasmosis does not show strong breed predisposition, with geographic exposure being far more important than breed in determining infection risk. Dogs of any breed living in or traveling to endemic areas can develop histoplasmosis when exposed to the organism. The disease has been reported in numerous breeds as well as mixed-breed dogs. Some studies have suggested higher diagnosis rates in sporting breeds, working breeds, and hounds, but this likely reflects lifestyle factors and outdoor exposure patterns rather than genetic susceptibility. Breeds commonly used for hunting or field work may have increased environmental exposure in endemic regions. The most significant risk factor remains living in or visiting areas where Histoplasma capsulatum is prevalent in the environment.

Certain categories of dogs face elevated risk regardless of breed. Young dogs, particularly those between one and four years of age, are diagnosed more frequently than older dogs in some studies. Dogs with extensive outdoor access, particularly those allowed to roam, dig, or hunt in endemic areas, face higher exposure risk. Working dogs, hunting dogs, and sporting breeds engaged in field activities have increased environmental contact. Immunocompromised dogs, including those receiving immunosuppressive medications for immune-mediated conditions or cancer chemotherapy, are at increased risk for severe disease if exposed. Dogs living in rural areas or on farms in endemic regions may have higher exposure than urban dogs.

Screening recommendations for histoplasmosis are based on clinical presentation and exposure history rather than breed-based screening. There are no routine screening tests recommended for healthy dogs, even in endemic areas. Dogs presenting with chronic respiratory signs, unexplained weight loss, chronic diarrhea, or other compatible clinical signs should be tested, particularly if they have lived in or traveled to endemic regions. Veterinarians in endemic areas maintain higher suspicion for histoplasmosis when evaluating dogs with chronic, unexplained illness. When a dog in a multi-dog household is diagnosed with histoplasmosis, other dogs with similar exposure may warrant evaluation if they show any clinical signs, though the infection is not contagious between animals.

Conditions commonly co-occurring with histoplasmosis primarily include immunocompromising conditions that may predispose to clinical disease following exposure. Dogs receiving immunosuppressive therapy for immune-mediated diseases or post-transplant management face elevated risk if exposed to Histoplasma. Dogs with hyperadrenocorticism, whether naturally occurring or iatrogenic, have impaired immunity and may be more susceptible to severe disease. Cancer and cancer chemotherapy compromise immune function and increase opportunistic infection risk. In some cases, diagnosis of histoplasmosis prompts investigation for underlying immunocompromising conditions. Secondary bacterial infections may complicate advanced histoplasmosis, particularly when bone marrow suppression impairs the dog's ability to fight bacterial pathogens.

Conditions producing similar clinical signs that must be differentiated from histoplasmosis include other systemic fungal infections. Blastomycosis, endemic to overlapping geographic areas, produces similar respiratory and disseminated disease. Coccidioidomycosis, found in southwestern states, causes comparable systemic illness. Cryptococcosis, though typically causing different clinical patterns, enters the differential diagnosis for systemic mycoses. For dogs presenting with chronic diarrhea and weight loss, inflammatory bowel disease, intestinal lymphoma, and other enteropathies must be distinguished from gastrointestinal histoplasmosis. Thoracic histoplasmosis must be differentiated from bacterial pneumonia, other fungal pneumonias, and pulmonary neoplasia.

Potential complications of histoplasmosis include progression to severe disseminated disease involving multiple organ systems. Bone marrow involvement can cause life-threatening anemia, thrombocytopenia, and leukopenia that predispose to secondary infections and bleeding. Severe gastrointestinal disease leads to malnutrition, hypoalbuminemia, and cachexia. Ocular histoplasmosis can result in permanent vision impairment or blindness. Respiratory failure may occur with severe pulmonary involvement. Treatment complications include azole antifungal hepatotoxicity and nephrotoxicity from amphotericin B. Disease relapse following apparently successful treatment can occur, particularly with inadequate treatment duration. Permanent organ damage may result from severe disease even after successful treatment of the infection.