The First Autochthonous Case of Actinomycetoma in a Bedouin Patient in the Israeli Negev Region

ABSTRACT.

We report the first autochthonous case of actinomycetoma in a Bedouin patient from Israel’s Negev Region. The patient presented with plantar and interdigital (web) nodular lesions. The time to diagnosis from the first medical contact was 4 years, and several treatment modifications were made until a satisfactory clinical response was achieved. This case underscores the potential underdiagnosis of mycetoma in nonendemic areas, the limited data regarding optimal treatment regimens, and the need for heightened clinical awareness.

INTRODUCTION

Mycetoma is a chronic, progressive, and destructive granulomatous infection that is defined by a triad of draining sinuses, tumor-like swelling, and “grains.” mycetoma is attributed to bacterial (actinomycetoma) or fungal (eumycetoma) pathogens. Typical patients are young males who often traverse barefoot and are thus prone to trauma from soil contaminated with the causative agents; hence, the foot is the most commonly affected site. The infection is endemic in tropical and subtropical regions, with a high prevalence within the “mycetoma belt,” which is demarcated by the latitudes of 15°S and 30°N,¹ although sporadic cases outside this area are reported.²

A recently published collection of all mycetoma cases reported in Israel from 1942 to 2015 identified 21 cases, of which five were suspected to be autochthonous. However, even in these cases, some patients were born in or traveled to endemic areas, even if this was deemed an unlikely source.³

We present the first autochthonous case of mycetoma from the Israeli Negev Region, which is an arid region in southern Israel with two distinct populations where roughly 25% of the region’s population is Bedouin and 75% is Jewish. These two populations have distinct epidemiological risk factors for infectious diseases.

CASE PRESENTATION

In late 2018, a healthy 41-year-old female patient consulted at a dermatology clinic. An examination revealed tender subcutaneous nodules between the toes and on the instep of her right foot, which were discharging yellow granules. The patient reported experiencing increased pain while walking or working, leading to unemployment. Consequently, she was referred for surgical excision of the painful nodules. The patient belongs to the Indigenous Bedouin population and resides in the Negev Region, which is a semi-arid area in southern Israel. The patient reported no travel history outside the country and minimal travel within Israel, almost exclusively inside the Negev Region. The patient did not have agricultural exposure but did report walking barefoot on occasion.

From January 2019 to June 2020, the patient underwent three excisional biopsies because of recurring nodules (Figure 1A). The initial pathology results were nonspecific until organisms compatible with Actinomyces were noted in the pathology report. After local progression and the emergence of new nodules (Figure 1B), the patient was hospitalized and treated with a course of first-generation cephalosporin followed by prolonged oral amoxicillin, but this failed to yield a satisfactory response.

Figure 1.

Clinical progression. (A) Early during the diagnostic process—small nodule on the instep and between toes one and two of the right foot. (B) Disease progression with enlargement of the nodules. (C) Partial resolution of the nodules during treatment.

Because of the poor response to treatment and clinical features incompatible with Actinomyces infection, a comprehensive workup was initiated. First, a repeat biopsy was performed, with the following findings: Hematoxylin and eosin (H&E) staining showed amorphous basophil structures surrounded by a dense inflammatory infiltrate consisting of histiocytes and neutrophils next to “grains” of organisms. Periodic acid–Schiff (PAS) staining was negative, and Grocott’s methenamine silver (GMS) staining emphasized thin filaments (Figure 2). Tissue fungal and bacterial culture results were negative. Eventually, a 16S polymerase chain reaction (PCR) test yielded a match to Actinomedura madurae. Magnetic resonance imaging of the foot (Figure 3) showed extensive soft-tissue involvement and several localized masses measuring ∼6 × 3 × 3 cm each, with no involvement of bone or joint.

Figure 2.

Histopathologic examination of the lesion. (A) On H&E at low power (original magnification 40×), there is a dense inflammatory infiltrate surrounding amorphous basophilic structures. (B) At higher power (original magnification 200×), there is a supportive infiltrate right in the neutrophils, particularly close to the “grains” of organisms, with prominent histiocytes. The grains have the classic filamentous appearance of Actinomyces spp. (C) On the PAS stain (original magnification 200×), they are negative, but on (D) the GMS (original maginification 400×), the bacterial filaments are highlighted. H&E = hematoxylin and eosin; GMS = Grocott’s methenamine silver; PAS = periodic acid–Schiff.

Figure 3.

Magnetic resonance image of the affected foot: soft-tissue involvement and several localized masses, with no involvement of bone or joint.

Treatment with trimethoprim/sulfamethoxazole (TMP-SMX) and rifampicin was initiated, but because of further clinical progression after 8 weeks, rifampicin was replaced with amikacin, with no significant response. Amikacin was later replaced with streptomycin TMP-SMX for 3 months, with nodule volume reduction and better tread ability (Figure 1C). After the complete resolution of the lesions, maintenance with Dapson monotherapy was initiated. Although a clinical cure for the foot lesions was achieved, unfortunately, the patient suffers from severe hearing loss, which is likely related to the prolonged course of aminoglycosides.

DISCUSSION

We present the first case of mycetoma in a Bedouin patient from the Negev Region, which is the most southern district of Israel. Our patient lives in a rural community and has never left Israel. Our case highlights the fact that mycetoma is endemic in the Negev area of Israel and could be underdiagnosed.

The presence of mycetoma in the Israeli Negev Region may be influenced by its semi-arid climate, which shares similarities with known endemic regions and potentially provides suitable conditions for the causative organisms. Moreover, many Bedouin communities in the area engage in traditional farming and animal husbandry, which could increase exposure to soil-dwelling pathogens.

Because of its nature as a slowly progressive granulomatous disease, the diagnosis of mycetoma is often delayed, and a 3-year gap between presentation and diagnosis, as seen in our patient, is not uncommon, especially in areas of low endemicity. This delay can lead to complications such as disability, secondary infection, and osteomyelitis. Although autochthonous cases of mycetoma have been reported previously in Israel,³ most have possible origins elsewhere, and the few truly local cases originated from other areas within the country.

Another challenge lies in microbiological diagnosis. Traditional culture-dependent methods can be unreliable in mycetoma, especially when the clinical suspicion is low and cultures are attempted from host tissue, not granules. In our case, the 16s PCR test shortened the time for an accurate diagnosis. However, this method is not readily available in most endemic regions. Newer diagnosis methods, such as directed PCR tests, are under development.⁴

The last challenge presented lies in selecting a treatment regimen. Low-quality data exist, comprised mostly of case reports and case series.⁵ Most (four of five) previously reported autochthonous Israeli mycetoma cases are bacterial (actinomycetoma), in contrast to areas such as Northern India, where most cases are fungal (eumycetoma).⁶ Our case, with bacterial etiology, was resolved with medical treatment, as is common with actinomycetoma. However, most cases of eumycetoma require surgery as part of the treatment to achieve a long-lasting cure.

Although TMP-SMX remains the cornerstone of mycetoma treatment, often combined with other antibiotics, our patient’s case demonstrates that treatment modifications may be necessary to achieve a satisfactory clinical response. The “Welsh regimen,” which combines TMP-SMX with amikacin in cycles, has shown efficacy in resistant cases.⁷ The prolonged nature of actinomycetoma treatment, often extending for months to years, necessitates close monitoring for adverse effects and treatment response. In our patient’s case, the extended use of aminoglycosides resulted in severe hearing loss, highlighting the potential for significant treatment-related morbidity. This is a potentially preventable complication with careful therapeutic drug level monitoring and audiometry exams.

After comparing our case to others reported from nonendemic regions, it was found that those cases often involved diagnostic delays, with one study noting an average 3-year delay between symptom onset and diagnosis.⁸ This underscores the challenge of recognizing mycetoma in areas where it is not commonly encountered. Although our case involved a Bedouin patient with no travel history, many reports from nonendemic areas involve immigrants or travelers from endemic regions.⁹ This highlights the rarity of truly autochthonous cases in nonendemic areas. Additionally, although our case, along with two other local cases, was caused by Actinomedura madurae, reports from Europe and the United States often involve different causative agents, reflecting the diverse epidemiology of mycetoma.

This underscores the global relevance of mycetoma and the importance of increasing awareness among healthcare providers in both endemic and nonendemic regions.

CONCLUSION

Mycetoma presents a diagnostic and treatment challenge, often requiring a multidisciplinary team. This case highlights these challenges and the need to consider the diagnosis, even in a low-endemicity setting or areas with no previously diagnosed cases.