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Abstract

  1. Top of page
  2. Abstract
  3. Case Presentation
  4. Discussion
  5. Declaration of Interests
  6. References

We present a case of progressive disseminated histoplasmosis in an immunocompetent traveler. Histoplasmosis was acquired in South America; its manifestations included prolonged fever, splinter hemorrhages, erythema multiforme, arthritis, and mediastinal lymphadenopathy. To the best of our knowledge no splinter hemorrhages had previously been reported in a patient with histoplasmosis.

Histoplasmosis is an uncommon disease in returning travelers. We present a case of progressive disseminated histoplasmosis with unusual clinical manifestations.

Case Presentation

  1. Top of page
  2. Abstract
  3. Case Presentation
  4. Discussion
  5. Declaration of Interests
  6. References

A 64-year-old previously healthy male was admitted for investigation of fever up to 39°C and night sweats that appeared 6 weeks prior to admission. The patient was an avid traveler, and participated in jogging and cycling nearly daily. Symptoms first appeared 7 days after a 1-week trekking tour in Jordan, 3 weeks after a 1-month tour in Bolivia and Brazil, and 6 months after a tour in Angola and Ethiopia. The patient had participated in white water rafting in Africa and jungle trekking in South America. There was no history of cave exploration or exposure to bats on either trip. On admission, fever, weight loss, conjunctivitis, and a rash involving the dorsal aspects of both hands were noted. As time passed, fever gradually decreased, but weight loss progressed, and splinter hemorrhages (Figure 1), polyarthralgia, and arthritis of the ankles and knees developed.

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Figure 1. Splinter hemorrhages.

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Blood count revealed mild normocytic anemia consistent with anemia related to chronic inflammatory disease. Blood chemistry showed mild hypoalbuminemia, but was otherwise unremarkable. Erythrocyte sedimentation rate was 50 mm/hour, and C-reactive protein 24 mg/L (normal level 0–5). Additional tests including angiotensin converting enzyme level and a complete rheumatic panel were normal. Abdominal and chest CT scan revealed hilar and mediastinal lymphadenopathy with several pulmonary nodules (Figures 2 and 3). Transesophageal echocardiography (TEE) showed no valvular abnormalities or evidence of vegetations.

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Figure 2. Mediastinal lymphadenopathy.

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Figure 3. Pulmonary nodule.

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The clinical diagnosis of erythema multiforme was supported by the findings of a skin biopsy. Blood and bone marrow cultures for bacteria and mycobacteria were sterile. Serologic tests for Q fever, Rickettsia, Brucella, Leishmania, HIV, Epstein–Barr virus, and cytomegalovirus were negative. Blood smears for malaria and Borrelia were negative as well. Ten weeks after the onset of symptoms a serologic test for histoplasmosis was submitted to the Centers for Disease Control and Prevention, but was inconclusive.

Biopsy of a mediastinal lymph node revealed necrotizing granulomas. Ziehl–Neelsen, silver and periodic acid-schiff stains were negative for mycobacteria and fungi. Culture and PCR for mycobacteria were negative. The lymph node pathology sample was cultured on Sabouraud dextrose agar slant. After fungal growth appeared on the agar, identification of the isolate was performed by a PCR assay targeting the large-subunit fungal ribosomal RNA gene, followed by direct sequencing and matching the resulting sequence with the National Center for Biotechnology Information database.[1, 2] The isolate was identified as Histoplasma capsulatum.

The patient was diagnosed as having progressive disseminated histoplasmosis (PDH), and was treated with oral itraconazole according to current guidelines.[3] Within 3 weeks all signs and symptoms resolved. On follow up visit, 5 months after treatment was initiated, the patient felt well and had resumed all regular activities.

Discussion

  1. Top of page
  2. Abstract
  3. Case Presentation
  4. Discussion
  5. Declaration of Interests
  6. References

Histoplasma capsulatum is a dimorphic fungus with a wide geographic distribution. It is most prevalent in the Mississippi and Ohio River valleys in the United States and in Central and South America. Histoplasmosis also occurs, albeit less commonly, in Africa, the Indian subcontinent, Southeast Asia, China, and Australia. In Africa, H capsulatum var. duboisii coexists with the H capsulatum var. capsulatum. Histoplasmosis is acquired through inhalation of the fungus, usually from contaminated soil. The presence of H capsulatum in the soil is strongly linked to the presence of bird and bat guano.[4]

There are three clinical syndromes of histoplasmosis: acute pulmonary histoplasmosis, cavitary pulmonary histoplasmosis, and PDH. The patient described in this case had a disseminated disease, but also pulmonary nodules. We have noted in the past that the distinction between disseminated disease and pulmonary disease is not always clear in returning travelers. Some studies suggest that histoplasmosis occurs predominantly in males.[4] The incidence, however, may be skewed because of association between histoplasmosis and travel, cave exploration, construction, and smoking, all of which were male-dominated activities in the past.

Histoplasmosis in the patient was probably acquired in South America. The most prominent risk factors for PDH are old age and immunosuppression. Unlike other forms of histoplasmosis, PDH is a multisystem disease characterized by constitutional symptoms and involvement of various organ systems.[5] Skin manifestations associated with histoplasmosis are maculopapular eruptions, petechiae, ecchymosis, erythema multiforme, and erythema nodosum.[6, 7] Such skin manifestations are more common with the South American H capsulatum variants. A study from Brazil suggests this is due to two specific H capsulatum strains typical to Latin America.[8, 9] African histoplasmosis, caused by H capsulatum var. duboisii, is different from “classic” histoplasmosis, and is characterized most commonly by skin and skeletal involvement.[4]

The patient had developed splinter hemorrhages during the course of his disease. Splinter hemorrhages are associated with vasculitis, which can be related to infectious and non-infectious diseases, and with certain drugs, trauma, high altitude, and old age.[10] We are unaware of any previous report of PDH associated with splinter hemorrhages. Although infective endocarditis is frequently associated with splinter hemorrhages, and has been reported in patients with histoplasmosis, it is unlikely to have occurred in this patient. In histoplasma endocarditis the left-sided valves are more commonly affected, and approximately half of the patients have prior valvular disease. Echocardiography usually shows extensive valvular lesions, and the disease is unlikely to respond promptly to medical treatment alone.[11] In this case, TEE revealed no vegetations or valvular abnormalities, and all symptoms and signs resolved promptly with medical treatment alone. In addition, the patient had no other disease or condition associated with splinter hemorrhages. We thus hypothesize that splinter hemorrhages can be a manifestation of disseminated histoplasmosis itself.

Diagnosis of histoplasmosis relies on culture, histopathology, serologic tests, and antigen detection,[12] although culture is considered the gold standard for confirmation. Because histoplasmosis is not endemic in Israel, our laboratory does not have sufficient experience with identification by culture, and we rely on the use of PCR to confirm the final diagnosis. Moreover serologic tests are known to be unreliable, especially in disseminated disease,[13] and culture yield is probably low in travelers,[12] emphasizing the need for faster and newer diagnostic strategies.

Histoplasmosis is uncommon among returning travelers, and mostly presents as a pulmonary disease. When histoplasmosis is encountered among travelers, it is commonly associated with cave exploration and appears in outbreaks associated with a common source.[14-18] However this is not always the case, and sometimes an environmental source of the infection is not found. Clinicians should therefore be aware of this uncommon infection and its various clinical manifestations in patients with the appropriate travel history.

Declaration of Interests

  1. Top of page
  2. Abstract
  3. Case Presentation
  4. Discussion
  5. Declaration of Interests
  6. References

The authors state they have no conflicts of interest.

References

  1. Top of page
  2. Abstract
  3. Case Presentation
  4. Discussion
  5. Declaration of Interests
  6. References