Grand Round
Facial Balamuthia mandrillaris infection with neurological involvement in an immunocompetent child

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Summary

Cutaneous infection by Balamuthia mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement. It often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Patients can be either immunocompetent or immunocompromised. It is probably transmitted via inhalation or inoculation through broken skin, and then spreads to the brain and other organs through haematogenous spread. It is important for clinicians to be aware of this disease because rapid diagnosis and subsequent therapy has, in some cases, been associated with survival. In this Grand Round, we report the case of a 7-year-old boy who presented with large, chronic plaques on his face. Several biopsies showed non-specific granulomatous inflammation. The patient deteriorated rapidly and died within 1 month of displaying abnormal symptoms in the CNS. Immunohistochemical staining of skin tissue identified B mandrillaris as the infectious agent. The diagnosis was confirmed with PCR, which detected B mandrillaris DNA in formalin-fixed skin tissue sections. B mandrillaris infection should be considered in the differential diagnosis of patients with chronic granulomatous lesions. We also reviewed the epidemiology, B mandrillaris in nature and in the laboratory, clinical manifestations, histopathology, diagnosis, and treatment of infection.

Introduction

Among free-living amoebae, which are widely distributed in nature, only four genera or species are known agents of human infection: Acanthamoeba spp, Naegleria fowleri, Balamuthia mandrillaris, and Sappinia pedata.1 Since its initial identification in 1986 during an encephalitis outbreak affecting primates at the San Diego Wild Animal Park in California, USA, B mandrillaris has been an increasingly recognised cause of amoebic encephalitis in human hosts. Over 300 cases have been reported worldwide.2, 3, 4 B mandrillaris has been isolated from soil, dust, and water, and it is probably transmitted via inhalation or inoculation through broken skin, and then spreads haematogenously to the brain and other organs.5 B mandrillaris is capable of infecting both healthy and immunosuppressed people.

B mandrillaris infection in humans is rare and usually has a fatal outcome. It has two kinds of clinical presentations: one is encephalitis without skin lesions, from which affected patients usually die within months; the other shows initial skin lesions followed by development of encephalitis several years later.6 Patients with the latter of these two presentations can be treated when only skin symptoms are present. Awareness of this type of infection might prompt the development of earlier diagnostic and therapeutic strategies, which will potentially improve clinical outcomes. Therefore, it is very important to recognise this disease and diagnose it correctly as soon as possible.

Here, we report on a 7-year-old boy with cutaneous granulomatous lesions and neurological manifestations. The patient deteriorated rapidly and died 1 month after showing symptoms of CNS involvement.

Section snippets

Case presentation

A 7-year-old boy presented with a 5-year history of indurated plaques on his face. There was a history of trauma to the forehead in December, 2013, after which the skin eruptions first appeared. He fell onto moist concrete ground in a courtyard and the wound on his forehead was given several stitches. The asymptomatic papules progressively enlarged around the trauma site. 5 years later, the lesions gradually developed into erythematous and markedly indurated rock-hard plaques. The patient had

Epidemiology

B mandrillaris was first isolated from a pregnant mandrill baboon that had died from subacute meningoencephalitis in 1986 at the San Diego Zoo, CA, USA. Cases of human infections have been reported since 1990.2, 7 More than 300 cases have been reported worldwide, predominantly in the USA, Peru, and China.4, 8, 9 The last review of cases by the CDC stated that a total of 109 cases of B mandrillaris had been reported in the USA between 1974 and 2016.8 The number of Peruvian cases since 1990 has

B mandrillaris in nature and the laboratory

The life cycle of B mandrillaris, like that of Acanthamoeba spp, includes a vegetative trophic stage and a dormant cyst stage. It exists in the pathogenic trophozoite form under favourable conditions and converts to the resistant cyst form when exposed to harsh conditions, such as food deprivation or extreme pH, temperature, or osmolarity.15 The trophozoite is 12–60 μm in diameter and is characterised by a round nucleus with a large, spherical, densely staining nucleolus. Binucleate forms are

Clinical manifestations

B mandrillaris infection has two different clinical presentations. One has been observed in patients in the USA, who directly developed encephalitis without skin lesions, and usually died within months. The other has been reported in patients from Peru and China, who showed initial skin lesions and developed encephalitis several years later.4 In the US case series, only 5% of patients had a cutaneous form of the disease, whereas the majority of patients in the Peruvian and Chinese case series

Histopathology

The common histopathological characteristics of B mandrillaris infection include diffuse granulomatous reactions on the reticular dermis, and surrounding infiltration rich in lymphocytes and plasma cells, and giant multinucleate cells. Recent studies in China have suggested that granulomatous inflammation with prominent infiltration of lymphocytes and plasma cells on the face is suggestive of the disease.4 A definitive diagnosis requires the detection of a trophozoite or cyst.3 In the Peruvian

Diagnosis

The diagnosis of B mandrillaris infection is still challenging because most dermatologists and neurologists are unfamiliar with the disease. Ancillary methods to corroborate the diagnosis include serology, special staining methods for skin and brain tissues, and molecular biology.

Serological methods include ELISA and indirect immunofluorescence assay. Previous studies have suggested that positive serology can be helpful for the diagnosis of B mandrillaris infection, but it does not always

Treatment

There is currently no established treatment for this disease, and the survival of afflicted patients is extremely rare.5, 26 It is now possible that medical therapies based on a combination of drugs, including an antiparasitic medication called miltefosine, can be offered to patients with isolated cutaneous lesions and those already displaying CNS involvement.39 Miltefosine, which was approved by the US Food and Drug Administration for the treatment of leishmaniasis in 2013, has also shown

Conclusion

In conclusion, we have reported on a 7-year-old boy with granulomatous lesions on the face and CNS involvement, which was finally confirmed as B mandrillaris infection with immunohistochemical staining and conventional PCR analysis of formalin-fixed paraffin-embedded tissue. Timely histopathological evaluation of free-living amoebae might mean the difference between survival and death for patients presenting with treatment-refractory localised granulomatous lesions. B mandrillaris infection

Declarations of interest

We declare that we have no competing interests.

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