Disseminated histoplasmosis

Disseminated histoplasmosis, also known as progressive disseminated histoplasmosis, is a severe form of histoplasmosis infection typically seen in immunosuppressed patients, especially in the setting of HIV infection. It results from haematogeneous dissemination of the infection, involving multiple organs and systems and associating a high mortality¹.

Terminology

Although it is sometimes referred to as extrapulmonary histoplasmosis, lung involvement is one of the commonest manifestations of this condition².

Epidemiology

Dissemination of the disease is fairly uncommon and may occur in 1 in 2000 acute infections³.

Risk factors

• HIV infection, especially with less than 150 cells/μL CD4^1,4. Disseminated histoplasmosis is considered an AIDS-defining illness.

• Immunosuppressive medications⁴

• Biologic agents (infliximab, etanercept)³

• Immune disorders (idiopathic CD4 lymphocytopenia, Job's syndrome, common variable immunodeficiency)⁴

• Extremes of ages⁴

Clinical presentation

Clinical presentation includes systemic symptoms such as fever, weight loss and fatigue and local systems depending on the organs involved, with frequent progressive shortness of breath and diarrhoea^1,3.

Physical examination may reveal hepatoesplenomegalyhepatosplenomegaly, lymphadenopathy and skin and oral lesions¹.

Location

• Lungs: parenchymal disease².

• Bowell: any site of the digestive tube can be involved, with potential bleeding or perforation^1,4.

• Liver and spleen: haemophagocytic lymphohistiocytosis with macrophage activation syndrome¹.

• Kidneys: granulomatous nephritis¹.

• Adrenal glands: adrenal insuficciencyinsufficiency^1,3.

• Central nervous system: meningeal, brain or spinal cord lesions¹.

• Skin¹

Radiographic features

Although multiple organs and systems can be affected, only pulmonarythoracic and abdominal manifestations have been described in detail.

PulmonaryThoracic

Chest radiographs show pulmonary abnormalities in about 50% of the patients². Diffuse multiple small nodules are the most common pattern, even though linear and irregular opacities or segmental, lobar or diffuse air-space opacities can also be observed^2,5.

CT demonstrates diffuse miliary nodules measuring 1-3 mm³. Pleural effusions and thoracic lymphadenopathy are uncommon^2,3. Calcified lymph nodes or granulomas are described in about one third-third of patients, indicating previous contact with the microorganism².

Abdominal

• Hepatoesplenomegaly (30-100%)^1,4,6.The spleen may show diffuse decreased attenuation (thought to be a specific finding) and splenic infarcts⁶.

• Lymphadenopathy (~66%)^4,6. Typically of homogeneous soft-tissue density, but they can also be of diffuse or central low attenuation⁶.

• Segmentary gastrointestinal inflammation that affects any site along the gastrointestinaldigestive tract, but in particular the terminal ileum (most common intestinal presentation). There may be associated ulcerations leading to perforation of the small or large bowel, as well as intestinal bleeding^1,4.

• Intestinal inflammatory masses mimicking colon carcinoma and potentially causing large bowel obstruction (less common intestinal presentation)^1,4.

• Adrenal glands enlargement (rare)^1,6.

• Pancreatic enlargement (rare(very rare)⁴.

• Cholecystitis (rare(very rare)⁴.

• Abdominal free fluid⁶.

Central nervous system

Occurs in 5-10% of patients, with focal mass-like lesions in the brain or the spinal cord with possible ring enhancement being the most common manifestation. Other less common features include meningitis, encephalitis, ischaemic lesions and hydrocephalus¹.

Treatment and prognosis

Initial treatment with liposomal amphotericineamphotericin B is recommended in the first two weeks, followed by a maintenance therapy with itraconazole for a minimum of 12 months^1,4.

Mortality without treatment reaches an 80%, but reduces to <25% when the appropiateappropriate drugs are administered⁴.

Differential diagnosis

For pulmonary involvement consider:

• Miliary tuberculosis^3,5

• Miliary metastases^3,5

• Miliary sarcoidosis³

For haematologic involvement with hepatosplenomegaly and lymphadenopathy consider:

• Lymphoma⁶

• Kaposi sarcoma⁶ (especially in AIDS patients)

• Hepatic and splenic tuberculosis (particularly if there are associated low-attenuation lymphadenopathys⁶ and pulmonary nodules)

• Mycobacterium avium-intracellulare infection⁶

For gastrointestinal involvement consider:

• Inflammatory bowel disease (particularly Crohn's disease due to the ileal involvement)⁴.

• Colon carcinoma when inflammatory masses are present⁴.

• Tuberculous ileitis (especially if there are also pulmonary findings).