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Presentation of Quiz #32

A 24 year old female was admitted to the hospital for evaluation of a skin lesion. One year prior to admission, the patient had noted a bruise on the right arm, which she indicated was from a bite from her child. Six months later, a pruritic pustule developed, ruptured, ulcerated and increased in size. Six weeks prior to admission, the patient began to vomit, have headaches on the right side and noticed a tender swelling below the jaw on the right side. Multiple cultures for bacteria and fungi were negative; however, several skin biopsy specimens showed chronic granulomatous inflammation. Although therapy with amphotericin B was instituted, the patient died of cardiac arrest on day 33.

The following images were taken of her arm:

Scans of the head showed contrast-enhanced lesions in the right hemisphere, a midline shift to the left and normal-sized ventricles. Results of a lumbar spinal tap showed a lymphocytosis.

Based on the current findings and the assumption that the causative agent is a parasite, what other diagnostic procedures could you recommend?

What organisms might you suggest as possible etiologic agents in this particular case? Provide reasons for each organism named as a possible cause.

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Answer and Discussion of Quiz #32

Answers to Questions:

  1. Assuming the possibility of infection with free-living amebae, diagnostic procedures could include direct wet preparations of CSF, necrotic brain tissue, review of the histologic preparations and histologic review of autopsy specimens. Agar plate cultures could also be set up for the recovery of trophozoites and cysts of Acanthamoeba.
  2. The protracted course in this case is characteristic of severe illness caused by Acanthamoeba, and distinguishes this disease from primary amebic meningoencephalitis (PAM), caused by Naegleria, which has a much more acute presentation. Additional features that helped to distinguish Acanthamoeba infection from that caused by Naegleria were the unusual skin lesions and the presence of significant lymphocytosis in the CSF in contrast to the predominantly PMN purulence of the CSF of patients with PAM.

Comments on the Patient: Prior to autopsy, a wet mount of the CSF mixed with necrotic brain tissue revealed amebic trophozoites (left). Although no cysts were seen, an image of the typical, double-walled cysts is included below (right):

Autopsy findings included granulomatous inflammation in the breasts, lungs, adrenal glands, thyroid gland and skin. The cribiform plate showed no abnormalities, but a purulent ethmoid sinusitis was noted. A rubbery mass was seen in the right temporal area of the brain, and grossly soft hemorrhagic lesions were seen throughout the cortex, white matter, basal ganglia, cerebellum and brainstem, which histologically revealed necrosis, acute vasculitis and chronic perivascular inflammation. It was also discovered at autopsy that the patient was pregnant with an embryo compatible with nine weeks' gestation.

Comments on the Infection: Disseminated Acanthamoeba Infection

An early diagnosis can be made if amebic infection is considered in patients with meningitis. Naegleria can be seen in a wet mount of CSF examined under low power with the condenser lowered to increase contrast. However, it is less likely to see organisms in CSF in patients with disseminated Acanthamoeba infection. The positive wet mount that was examined from this patient was a mix of CSF and necrotic brain tissue obtained at surgery; this particular specimen revealed motile amebic trophozoites.

Skin lesions in patients with Acanthamoeba infection have been reported previously. In each case, organisms resembling Acanthamoeba were ultimately found in histopathologic specimens. The presence of a persistent skin lesion with negative stains and cultures for bacteria and fungi should alert clinicians, pathologists, and microbiologists to the possibility of disseminated Acanthamoeba infection.

Comments on the Organism: Acanthamoeba have been found in the upper respiratory tract in humans with and without symptoms. In cases of disseminated disease the portal entry remains unknown, but is suspected to be the respiratory tract. However in patients with skin lesions, the skin may be the site of primary inoculation. Although many of the reported cases have been seen in compromised patients, cases have also occurred in immunologically competent hosts. In spite of the fact that this patient was pregnant (altered immune state), the patient history indicates that dissemination occurred prior to conception.

Although Naegleria dissemination outside the central nervous system may occur, it is apparently rare and unlike the protracted situation seen in this patient. The morphology of Naegleria trophozoites is quite different from Acanthamoeba and an image can be seen below (wet mount). Note the lobular pseudopodia as compared with the "spiky" pseudopodia seen in Acanthamoeba trophozoites above.

Therapy: Current therapy for Acanthamoeba meningoencephalitis includes amphotericin B and sulfadiazine or sulfisoxazole or pentamidine isethionate. Treatment is somewhat problematic and amphotericin B may be ineffective. Skin ulcers have been treated with systemic administration of combination therapy pentamidine isethionate IV for one month and oral itraconazole for eight months. The skin ulcers can also be cleaned twice daily with chlorhexidine gluconate solution and treated with topical application of 2% ketoconazole cream.

References

  1. Garcia, LS, 2016. Diagnostic Medical Parasitology, 6th Ed., ASM Press, Washington, DC.
  2. Special thanks to Dr. George Healy (retired) from CDC for the case information and images.

The original case was presented by:

  1. Gullett, J. et al. 1979. Disseminated granulomatous Acanthamoeba infection presenting as an unusual skin lesion. Amer. J. Med. 67:891-895