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Case Report *Corresponding author Aksone Nouvong, Department of Surgery, Olive View UCLA Medical Center, 14445 Olive View Drive, Sylmar, Early Presentation of CA 91342, USA, Tel: 1-747-210-3194; Email: ANouvong@

Submitted: 30 June 2017 Subcutaneous Accepted: 16 August 2017 Published: 18 August 2017 in the Lower Extremity ISSN: 2475-9112 Copyright David Aungst1, Raffi Salibian2, Oran Schachter3, Armine Baltayan4, © 2017 Nouvong et al. and Aksone Nouvong5* OPEN ACCESS 1Surgical & Perioperative Careline, Olive View UCLA Medical Center and DVA Greater Los Angeles, USA 2Olive View UCLA Medical Center and David Geffen School of Medicine at UCLA, USA 3Department of Medicine, Olive View UCLA Medical Center and DVA Greater Los Angeles, USA 4Department of Pathology, Olive View UCLA Medical Center, USA 5Department of Surgery, Olive View UCLA Medical Center, USA

Abstract We present a case of eumycetoma with aspergillus as a causative organism. The patient presented at an early stage and was successfully treated after a combination of surgical excision and medical treatment. A high index of suspicion should be present when patients present with a soft tissue mass and risk factors such exposure of to soil and country origin from the “ belt”. Tissue and culture should be completed. It is important to catch the infection at an early stage, as it will determine the prognosis and avoid devastating outcome.

INTRODUCTION Mycetoma is a chronic infection of the subcutaneous tissue period in the subcutaneous layer. The mass can get fixed and caused by either Actinomycetoma bacteria (actinomycetoma) ultimately develops a sinus tract that will penetrate the skin and or fungal (eumycetoma). The result of the infection is a drainThere purulent are material several methodswith grains for [3]. diagnosis. The different granulomatous inflammatory response in the subcutaneous or Thecausative color and agent texture can beof the identified discharge by grain visually can inspecting be suggestive the bydeep Colebrook dermis. inWhen 1946 actinomycetoma to describe an abnormal or eumycetoma growth occursthat was in drainage, microscopically evaluating the organism or by culture. frequentlythe foot it is noted termed on Madura feet of nativesfoot. Madura of the foot Madurai was first District coined in of specific organisms [9]. However, it is often difficult identify the belt between latitudes 30°N and 15°S, which is commonly the specific causative agent as these organisms are very slow calledIndia [1,2]. “the mycetomaMycetoma commonly belt”. This affects belt includes population Sudan, who Somalia, live in growing and are easily contaminated [10]. When discharge is Senegal, India, Yemen, Mexico, Venezuela, Columbia, Argentina not present, a punch biopsy to the subcutaneous level or local and other surrounding countries [3-5]. The most common cause excision with histopathological examination is the next step. Under the microscope, Eumycetoma shows branching septate of mycetoma in the United States is due to Pseudallescheriaboydii hyphae with extensive surrounding suppurative granulomas and fibrotic reaction. Actinomycetoma shows poorly defined [3]. However, the prevalence is unknown as this condition filamentous structures with variable size granules [11]. A more contactusually and presents work inwith immigrant soil. As a result, who came the clinical from countries manifestations listed organismsuperior method [12]. for analysis is polymerase chain reaction, which areabove. frequently This condition seen on usually lower affects limb (82%) field workers and hands who (7%) come [6]. in can provide rapid diagnosis and identification of the causative

Treatment options for mycetoma are optimally a combination resourcesToday, the and World international Health Organization attentiveness considers [7]. mycetoma as a of medical and surgical therapy. Medical treatment is usually neglected tropical disease and attributes this problem to lack of dividedoptimized into after two identification dosages of 200 of causative mg every organism. morning andIn case every of Eumycetoma, the gold standard is 400 mg per day, Clinically, the patient will be asymptomatic during the incubation period that can last several weeks to months [8]. The evening. The duration of this treatment depends on clinical sequelae include a tumefaction process, which is a tumor-like response and side effects, but ranges from 9 to 18 months [9,13- mass that is usually painless and develops during the incubation 15]. Benefits of triazoles, such as itraconazole and , Cite this article: Aungst D, Salibian R, Schachter O, Baltayan A, Nouvong A (2017) Early Presentation of Subcutaneous Aspergillus Infection in the Lower Extremity. JSM Foot Ankle 2(4): 1034. Nouvong et al. (2017) Email:

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from the soft tissue lesion. He denied any discharge, enlargement is that they help to localize the disease by encapsulating the to clinic with complaints of occasional pain and pinpoint bleeding sulfamethoxazolelesion, which later for assists 6 months in easier to 2Years. excision. If there In is uncomplicated lack of clinical actinomycetoma the primary treatment is with trimethoprim- of mass or constitutional symptoms. On exam, the lesion size was unchanged compared to previous visits (Figure 2). However, response, amoxicillin-clavulanic acid can be used for 6 months. In there was newly noted pinpoint bleeding from multiple areas more severe cases with lack of response to the above treatment, of the lesion beyond the biopsy site. There was no erythema or combined treatment of amikacin for 3 weeks with trimethoprim- increased warmth. Based on the new findings, patient agreed to sulfamethoxazole for 5 weeks is indicated. This cycle is repeated proceed with an incisional/excisional biopsy. until complete cure is achieved. Local wide excision is useful The intraoperative findings noted a firm multilayered soft when there is lack of response to medical treatment or in early stages of infection or if there is bony involvement and often tissue mass with loculated septae extending into the fourth stages of the infection. Amputation is reserved for advance subcutaneous tissue surrounding the soft tissue mass. Clear interspace of the left foot. Black debris was present in the serves as a lifesaving procedure [16]. We will present a case drainage was noted but no pus or purulence found. A 4.0x4.0x3.1 of eumycetoma in the foot caused by aspergillus and different cm soft tissue mass (Figure 3) was sent to pathology. clinicalCASE PRESENTATIONpresentations of subcutaneous and cutaneous infection. unremarkable, but cut sections through soft tissue showed a few The pathology report read that the skin surface was grossly

46-year-oldMexican-American male presented with a 10 scattered darkly pigmented pinpoint spots, 1-2 mm each, in the years’ history of a soft tissue mass on the dorsolateral aspect background of a yellow adipose tissue (Picture 1). No definitive of his left foot. He reported occasional itching and irritation in mass lesion was seen. Microscopically, many micro abscesses and closed toed shoes. He noticed progressive growth of the lesion necrotizing granulomas were present in the deep subcutaneous mainly in the past 7 months. He denied any history trauma or tissue, with associated pigmented structures, consistent with any open wounds on his foot. He also denied any drainage from fungal colonies (Picture 2). High power view of these colonies the lesion or pain. He has not received prior medical treatments. showed innumerable pigmented fungal hyphae with septation The patient hadan unremarkable past medical histories, which (Pictureand sharp 4). angle Grocott branching Methenamine (Picture Silver 3). Many (GMS) granulomas histochemical had medications.are negative forHe immunehad no known compromised drug allergies, state or family prior history infection of palisading histolytic and multinucleated giant cell reaction majorhistory. illnesses, At the time or history of his ofpresentation, any surgeries. he was He didnot nottaking smoke, any drink or use illicit drugs. He was born in Guadalajara, Mexico, and stain for fungal organisms was confirmatory (Picture 5). moved to California about 10 years ago. He worked as a gardener.

On physical exam, he was well nourished, well developed and in no apparent distress. His vital were stable. His lower extremity physical exam revealed the presence of a ~ 4cm x 5 cm soft tissues mass on the dorsal aspect of his 3-5th metatarsophalangeal joint. The lesion was firm, non-mobile with hyper pigmentation. There was no open lesions or drainage noted. The lesion did not Trans illuminate. No erythema or increased warmth noted peri-lesion. However, the lesion was mildly painful on direct palpation. His Figure 1 foot pulses were palpable and light touch sensation was intact. deformities of his foot/ankle noted. He had no inguinal or Coronal (a) and axial (b) fluid sensitive fat-saturated MR images of There were no pain with range of motion or no gross structural the foot at initial presentation. A loculated infiltrative soft tissue mass detected in the dorsolateral soft tissues of the forefoot with numerous cystic appearing popliteal lymphadenopathy. No other similar lesions were noted spaces within the lesion. The mass shows heterogeneous contrast enhancement on his upper extremities or trunk. (not shown). No MRI evidence for intra-osseous involvement. His initial radiographic findings were consistent with a non-specific dorsolateral forefoot soft tissue prominence (not shown). No calcification noted within the soft tissue mass on the radiograph. Magnetic resonance imaging (MRI) revealed a loculated infiltrative soft tissue mass in the dorsolateral forefoot withThe numerous case was internal discussed cystic-appearing with the spaces service.(Figure1). Patient underwent an incisional biopsy, obtaining a 0.5cm specimen. The intraoperative report noted a fibro fatty tissue with no evidence of grains, discharge or vasculature involvement. The pathology report noted fibrotic tissue with patchy acute and chronic Figure 2 inflammation, granulation tissue and a few multinucleated giant cells. Findings were discussed with the patient, who wished to Clinical presentation after second follow up. just monitor the lesion. However, 4 months post-op, he returned JSM Foot Ankle 2(4): 1034 (2017) 2/5 Nouvong et al. (2017) Email:

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Figure 3

Soft tissue mass excised with loculated appearance. Picture 4 giant cell reaction. Many granulomas with palisading histolytic and multinucleated

Picture 1

Scattered darkly pigmented pinpoint spots, 1-2 mm each, in the background of a yellow adipose tissue. Picture 5 Grocott Methenamine Silver (GMS) histochemical stain shows fungal organism.

Infectious disease was consulted due to concerns for

Eumycetoma. The patient completed a course of itraconazole 200 mg bid for approximately 8 weeks. An MRI was performed 5 weeks post excisional biopsy, which showed subcutaneous edema consistent with postoperative finding, no fluid collections or bony involvement noted (Figure 4). Three months postoperative exam showed complete healing of his tissue uneventfully without furtherDISCUSSION recurrence or other pedal complaints. Picture 2 There are more than 30 known causative agents of mycetoma Micro abscesses and necrotizing granulomas were present in the with fungal colonies. deep subcutaneous tissue, with associated pigmented structures, consistent and subcutaneous aspergillus (SA) is one of these many types [17]. This type of infection differs from the cutaneous form of , which is a sub type of fumigatus, a more common A. flavus, and A. niger,widespread A. terreus, disease and called A. nidulans invasive [18]. aspergillosis In SA the (IA).most The common most common organisms ofA. IA nidulans are Aspergillus [3] and A. flavus [19]. Both are

reported types of are rare with unknown prevalence. different than the subcutaneous form. Similar to other causative The clinical manifestation in cutaneous aspergillosis (CA) is

organisms of mycetoma, SA will present clinically with a triad of tumefaction, fistulation of abscess and extrusion of colored grains origins.[3]. Specifically, Primary inskin aspergillosis, lesions are usually the grains caused will by be intravenous white [20]. Picture 3 Cutaneous aspergillosis can be of either primary or secondary angle branching. access site, trauma, burns or surgery. Secondary skin lesions Innumerable pigmented fungal hyphae with septation and sharp usually result from a contiguous extension to the skin from a

JSM Foot Ankle 2(4): 1034 (2017) 3/5 Nouvong et al. (2017) Email:

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mycetoma [23-25]. However, radiological presentations are not specific to one organism, but rather has a general appearance thatAs is seen discussed all type earlier,of mycetoma. the gold standard treatment of

treatment for CA that is secondary to disseminated infection, the Infectiouseumycetoma Diseases including Society SA is of Itraconazole. America recommends In comparison, systemic the

as the primary therapy. Alternative agents include liposomal amphotericin B, posaconazole, itraconazole, Figure 4 caspofungin or micafungin [26]. availability of antimicrobial treatment and adequate surgical (a,b): MRI 5 week’s status post soft tissue excision. The prognosis of mycetoma depends on the stage of infection, third world and western countries. The recurrence rate varies excision. As a result, the prognosis will vary significantly between deep wide spread infection or blood-borne infection that seeds to the skin. The respiratory tract is the most common portal of from 25-50% and can be local or distant at the regional lymph entry. Other portals include the cornea, ear and damaged skin nodes [13]. A study in Sudan investigated the prognostic factor [18]. In CA, the initial skin presentation may be macular, papular, for healing and amputation in actinomycetoma and eumycetoma. nodular or plaque. Pustules are less common and may be seen a fever, swelling, in duration and tenderness. In secondary Their findings of eumycetoma cases (N=1242), 321 (25.9%) were in neonates. In primary infection, the patient will present with cured, 35 (2.8%) had amputations and 671 (54%) were dropped from the study due to various reasons. One of these reasons was infection, the lesion will initially appear as erythematous macule toxicity, gynecomastia and skin discoloration. They showed that dissatisfaction with side effects from triazoles such as hepatic [18,21].that can later develop into hemorrhagic bullae or ulcerative and might present similarly to pyoderma gangrenosum medical treatment was a predominant factor in determining medicalhealing ofand actinomycetoma. surgical treatment, On where the otherthe size hand, of the eumycetoma lesion was Subcutaneous and cutaneous aspergillus also differs in risk therapy outcome was more depended upon combination of factors: Most cutaneous occur in immune compromised patient such as those with HIV/AIDS, neonates, cancer patients, an important factor: patients with lesions greater than 5 cm had riskand recipientfactors that of aretransplant associated tissue with or CA,organs. such The as minor same traumarisk factors due a higher chance for undergoing amputation [27]. also apply to subcutaneous infections. However, there are other A retrospective study in France aimed to provide prognostic data regarding primary and secondary cutaneous invasive to prick or abrasion, walking barefoot, and working in agriculture aspergillosis. The number of subjects was 5 primary cutaneous or farm environment with exposureto soil [4]. malignanciesinvasive aspergillosis were the main (PCIA) the andunderlying 10 secondary condition cutaneous for these The radiographic presentation of IA depends greatly on subjectsinvasive (12/15). aspergillosis All 5 PCIA (SCIA), subjects totaling were treated of 15. with Hematological the anatomic source of the infection. Since most IA patients present with pulmonary disease, chest x-ray and computerized tomography (CT) can be utilized in the diagnosis of IA. The therapy and 2 of the 5 had surgical removal of skin necrosis. Six of cutaneous form rarely invades into deep layers when it presents PCIAthe 10 and SCIA 30% subjects for SCIA. were They treated concluded with antifungal that early therapy diagnosis based of in the limbs. The use of radiographic imaging such as x-ray, CT or in skin culture findings. The three-month survival was 100% for MRI is not commonly utilized in the diagnosis of the disease and the primary diagnosis occurs through skin biopsy. mostlyPCIA was in lungsassociated and brain with [27].better prognosis. In addition, survival in SCIA remains poor compared to PCIA due to vascular invasion In SA, the disease is more localized but tends to spread CONCLUSION vertically within a specific location. Diagnostic tools such as x-ray, MRI and CT scan can support with diagnosis. On x-ray, early stages appear as a dense shadow that can represent a wasWe successfully present atreated case ofafter eumycetoma a combination with of surgical aspergillus excision as a stage,granuloma. there As is the formation disease of develops cavities there with normalis periosteal bone reaction density. andcausative medical organism. treatment. The patient presented at an early stage and Inthat the is seen terminal as Codman stage, theretriangle will and be sun bone ray lysisappearance. with “melting In late snow appearance” [3,13,22]. Computed tomography and MRI skinA to high soil indexand country of suspicion origin shouldfrom the be “mycetoma present when belt”. patients Tissue are diagnostic tools that provide better visualization and extent present with a soft tissue mass and risk factors such exposure of of the infection. Computed tomography is more sensitive than MRI in early stages and demonstrates soft tissue infiltration, andbiopsy avoid and devastating culture should outcome. be completed. It is important to catch osteolysis and irregular periosteal reaction. The benefit of MRI the infection at an early stage, as it will determine the prognosis is that it provides information regarding the depth and extent of REFERENCES tissue invasion, which aids in surgical planning. In addition, MRI 1. presents with a classic dot-in-circle sign: a 2.5 mm hypointense foci that indicates the presence of grains and is highly specific for Gammel JA, Miskdjian H, Thatcher HS. Madura Foot (Mycetoma) the JSM Foot Ankle 2(4): 1034 (2017) 4/5 Nouvong et al. (2017) Email:

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