Background:
Mucormycosis is a rare but life-threatening infection, caused by fungi of the Mucorales order, which can be found in soil, rotting leaves or on animals. Through characteristic angioinvasive growth, infections with mucor spores can occur as a pulmonary, rhinocerebral or cutaneous form. Infections mainly affect immunosuppressed patients with a history of uncontrolled diabetes or haematological malignancies, among others. Treatment is multimodal and requires an immediate combination of intravenous amphotericin B therapy and serial surgical debridements. Only a limited number of cases of cutaneous mucormycosis of the hand have been documented and described previously.

Case presentation:
We report a cutaneous mucormycosis in an elderly patient with a therapy-resistant acute myeloid leukaemia after a minor trauma on his right hand, sustained whilst gardening. The fungal infection was treated with serial radical debridements, vacuum-assisted negative-pressure wound closure technique and intravenous antifungals. Despite successful eradication of the fungal infection, a palliative open wound care concept was implemented during the terminal course of the patient's leukaemia.

Conclusions:
Cutaneous mucormycosis is a rare but fulminant fungal infection mostly affecting immunosuppressed patients. Survival is possible when diagnosed and treated early, yet mortality rates remain high

Maleitzke, Tazio

Märdian, Sven

Stahnke, Katharina

Trampuz, Andrej

English

Institutional Repository of the Freie Universität Berlin

Contents lists available at ScienceDirectTrauma Case Reportsjournal homepage: www.elsevier.com/locate/tcrCase ReportA case report of cutaneous mucormycosis of the hand after minortrauma in a patient with acute myeloid leukaemiaTazio Maleitzkea,b,c,⁎, Katharina Stahnkea, Andrej Trampuza, Sven Märdianaa Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germanyb Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germanyc Berlin Institute of Health (BIH), 10178 Berlin, GermanyA R T I C L E I N F OKeywords:Cutaneous mucormycosisFungal infectionMucoralesImmunosuppressionLeukaemiaA B S T R A C TBackground: Mucormycosis is a rare but life-threatening infection, caused by fungi of theMucorales order, which can be found in soil, rotting leaves or on animals. Through characteristicangioinvasive growth, infections with mucor spores can occur as a pulmonary, rhinocerebral orcutaneous form. Infections mainly affect immunosuppressed patients with a history of un-controlled diabetes or haematological malignancies, among others. Treatment is multimodal andrequires an immediate combination of intravenous amphotericin B therapy and serial surgicaldebridements. Only a limited number of cases of cutaneous mucormycosis of the hand have beendocumented and described previously.Case presentation: We report a cutaneous mucormycosis in an elderly patient with a therapy-resistant acute myeloid leukaemia after a minor trauma on his right hand, sustained whilstgardening. The fungal infection was treated with serial radical debridements, vacuum-assistednegative-pressure wound closure technique and intravenous antifungals. Despite successfuleradication of the fungal infection, a palliative open wound care concept was implementedduring the terminal course of the patient's leukaemia.Conclusions: Cutaneous mucormycosis is a rare but fulminant fungal infection mostly affectingimmunosuppressed patients. Survival is possible when diagnosed and treated early, yet mortalityrates remain high.BackgroundMucormycosis is an invasive and rapidly progressing fungal infection caused by Mucorales organisms of the Zygomycota family.The ubiquitous filamentous fungi (molds) are frequently present in soil, decaying plants and on animals. More than 200 speciesbelong to the Mucorales order, including Sporodiniella, Syzygites, and Rhizopus of the Rhizopodaceae family [1]. Mucormycosis pre-dominantly affects immunosuppressed patients suffering from haematological malignancies, advanced human immunodeficiencyvirus (HIV) infection or uncontrolled diabetes mellitus. Infections include pulmonary, rhinocerebral, cutaneous or disseminatedmanifestations. First-line treatment consists of intravenous antifungal therapy with liposomal amphotericin B and radical surgicaldebridement. High morbidity and mortality are related to the high virulence of the fungus, its resistance to innate host defence and itsangioinvasive growth, which leads to tissue necrosis and haematogenous dissemination [2]. The median time from first symptoms tohttps://doi.org/10.1016/j.tcr.2019.100221Accepted 6 July 2019⁎ Corresponding author at: Charité - Universitätsmedizin Berlin Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353 Berlin,GermanyE-mail address: tazio.maleitzke@charite.de (T. Maleitzke).Trauma Case Reports 23 (2019) 100221Available online 15 July 20192352-6440/ © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).diagnosis is two weeks, and mortality rates range from 22% in the cutaneous to 79% in the disseminated form [3].Case presentationWe report the case of a 78-year old patient who presented to our surgical emergency department with swelling, erythema andpain of the back of his right hand, accompanied by a progressing hematoma located between the third and fourth metacarpopha-langeal joint (Fig. 1A). First signs of erythema and swelling manifested three days earlier, after a minor laceration, inflicted whilstgardening. Local incision and debridement were performed in another hospital and the patient was referred to our hospital because ofprogressive signs and symptoms of a local infection. The patient was previously diagnosed with a therapy-resistant acute myeloidleukaemia (AML) (46, XY, del(20)(q11.2)(18)/46, XY(3)) for which he received platelet and erythrocyte concentrates on a weeklybasis. AML was diagnosed ten months earlier as a transformation from a known myelodysplastic syndrome.Upon admission, the patient's C-reactive protein (CrP) level was increased at 41.6 mg/l [< 5mg/l], his leukocyte count was 3.47/nl [normal range, 3.90–10.50/nl] and his thrombocyte count was 17/nl [normal range, 150–300/nl]. After wound inspection, sterilewound dressings were applied, the patient's forearm and hand were immobilized in a cast, and treatment with intravenous ampicillinand sulbactam was initiated. At this time no indication for surgery was given, as clinical findings were consistent with a localizedsuperficial infection. Within the next 12 h however, clinical symptoms worsened, and the antibiotic strategy was changed to pi-peracillin-tazobactam combined with clindamycin. Under the assumption of a progressive phlegmon of the hand at post-admissionday (PAD) one, the patient underwent surgery. A thorough debridement and wound irrigation, via a dorsal incision, were performed.At the same time multiple samples for microbiological and histological analyses were harvested. Primary wound closure with twodrains was achieved (Fig. 1B).On PAD three, local swelling and infectious parameters increased (CrP of 159.6mg/l, leukocyte count of 4.78/nl), and revisionsurgery was performed on PAD four (Fig. 1C). One day later, microbiological results from the first surgery revealed an infection withRhizopus species (spp.) and thus the diagnosis of a cutaneous mucormycosis was confirmed. Intravenous amphotericin B treatment wasinitiated immediately and further debridements were planned. In addition, growth of Staphylococcus epidermidis was observed in thesame samples and clindamycin was stopped. Histopathologic analysis followed and showed proof of angioinvasive mucormycosis(Fig. 4). On PAD six, a second revision surgery was performed due to progressing local skin necrosis (Fig. 2A). A computed tomo-graphy scan of the thorax and abdomen on PAD seven, revealed suspicious lymph nodes of the mediastinum, but acquired biopsiesshowed no signs of a pulmonary fungal infection. The following day (PAD eight), the patient received a third revision operation(Fig. 2B) with the application of vacuum-assisted negative-pressure wound closure technique (Fig. 2C). Intraoperatively collectedtissue samples showed remaining fungal hyphae and Staphylococcus epidermidis in three specimens and intravenous vancomycin wasadded. All tissue samples harvested from subsequent revision surgeries (PAD 10, 14, 17 and 21) did not show any further fungal orbacterial growth.Fig. 1. PAD zero, initial clinical presentation in emergency department (A). PAD one, first surgery, postoperative finding (B). PAD four, first revisionsurgery, intraoperative finding prior to debridement (C).T. Maleitzke, et al. Trauma Case Reports 23 (2019) 1002212Granulation tissue formation was observed from PAD 10 onwards, following further elective revision surgery (Fig. 3A). On PAD11 the patient's respiratory function decreased rapidly, and extensive bilateral pleural effusions were observed on chest x-rays. Thepatient was transferred to the intensive care unit and two thorax-drains were placed for therapeutic thoracentesis, upon which thepatient's respiratory function improved. However, his general condition worsened notably over the following days, despite the factthat further revision surgeries revealed clean and vital wound conditions on PAD 14 (Fig. 3B), 17 and 21 (Fig. 3C).Fig. 4. Periodic acid–Schiff stained sections showing angioinvasive growth of Rhizopus spp. at a magnification of 200 (A) and 400 (B). M: mu-cormycosis, V: blood vessel.Fig. 2. PAD six, second revision surgery, intraoperative finding during debridement (A). PAD eight, third revision surgery, intraoperative findingprior to debridement and application of a vacuum-assisted negative-pressure wound closure technique (B). PAD eight, third revision surgery,postoperative finding after application of vacuum-assisted negative-pressure wound closure technique (C).Fig. 3. PAD 10, fourth revision surgery, preoperative finding with beginning granulation tissue formation (A). PAD 14, fifth revision surgery,preoperative finding (B). PAD 21, seventh revision surgery, preoperative finding (C). PAD 31, five days after removal of extensor tendons on PAD 25(D).T. Maleitzke, et al. Trauma Case Reports 23 (2019) 1002213At this stage, the patient and his relatives decided to decline further curative surgeries due to the underlying comorbidity and hisgeneral condition. In accordance with the patient's will, we removed the exposed extensor-tendons of the hand on PAD 25 as apalliative approach, allowing further soft-tissue granulation without further surgery. Fig. 3D shows a postoperative picture on PAD31, six days after removal of the extensor tendons. At this point, the patient's general condition worsened further, and signs ofpulmonary exhaustion and delirium were evident. On PAD 33 the patient died in the presence of his relatives due to his underlyingcondition.Discussion and conclusionsCutaneous mucormycosis of the hand is rarely reported and amputation of the hand and death are common complications of thisfulminant fungal infection [4–6]. The fungal infection is caused by members of the Mucorales order, which consists of mostly sa-protrophic organisms [1]. Cutaneous mucormycosis manifests predominantly in immunocompromised patients following minortrauma due to direct spore inoculation of exposed wounds. Risk factors include hematologic disorders, diabetes mellitus, gluco-corticoid therapy, intravenous drug abuse, renal failure and neutropenia [5]. Yet, infections with Rhizopus spp. of the hand and foothave also been reported in immunocompetent patients [5,7]. The described case herein demonstrates a progressive cutaneousmanifestation of Rhizopus mucormycosis after a minor laceration sustained whilst gardening, in a highly immunocompromised pa-tient with a therapy-resistant AML.The time between first local symptoms and diagnosis of mucormycosis has been reported to be around two weeks by Lanternieret al. [3]. In our case, Rhizopus mucormycosis was diagnosed nine days after the patient's first symptoms occurred. Rhizopus spp. is amold, found predominantly in soil and decaying plants, which fits well with the patient's history of gardening, before first symptomsoccurred [1].Diagnosis of cutaneous mucormycosis can be difficult as initial symptoms are often non-specific and can mimic a variety ofinfectious skin diseases. This underlines the utmost importance of early harvesting of soft-tissue probes from the lesion site in cases ofprogressive signs of infection. Following the guidelines [8], intravenous administration of liposomal amphotericin B and radicalsurgical debridement were started immediately upon the diagnosis of suspected mucormycosis. Surgical care included the applicationof a vacuum-assisted negative-pressure wound closure technique to cover the soft-tissue defect and to enhance soft-tissue granulation.This therapy has successfully been used previously to obtain a clean wound with granulating tissue in cutaneous mucormycosis [9].Fungal hyphae were found until PAD 8 in the intraoperatively collected tissue samples. However, all further biopsies revealed sterilespecimen, indicating successful treatment.Bearing the patient's underlying condition and the stress of repetitive surgeries in mind, his decision to decline any furthersurgical interventions was accepted, and a palliative solution was chosen together with the patient and his relatives. As furtheroperations, including a potential skin graft transfer or partial amputation, were abandoned, resection of the extensor tendons of thehand and open wound care were agreed to. Tendons represent a bradytrophic, poorly vascularized tissue with little healing qualitydue to avascular superficial zones, which are mainly nourished by diffusion [10]. In order to implement a feasible open wound careconcept, removal of tendons was inevitable and agreed to by the patient.If the patient had continued treatment and the wound had shown progressing granulation, a muscle flap transfer or skin grafttransfer would have been a possible surgical solution to cover the excessive skin and soft-tissue defect. This was reported previouslyas a successful treatment option in a case of cutaneous mucormycosis of the forearm with extensive soft-tissue defects due to radicalsurgical debridement [4]. If necrosis had progressed, a full or partial amputation of the hand would have been advised, as previouslydescribed by Lidor et al. in a case report of cutaneous Rhizopus oryzae mucormycosis after a burn injury [11].The aggressive course of the fungal infection presented here displays that, in spite of early diagnosis, a clear treatment algorithmis absolutely crucial to reach clinical and paraclinical improvements and to potentially achieve survival or limb salvage in patientssuffering from cutaneous mucormycosis. However, in immunosuppressed patients suffering from diseases like AML or HIV infectionthe general condition is often poor. Manifestation of mucormycosis usually appears at a late or terminal stage of the underlyingdisease and a fatal course may often not be possible to abrogate, regardless of early diagnosis and successful mucormycosis treatment[12,13]. Hence, a high level of suspicion for mucormycosis infections should be maintained in immunocompromised patients withcutaneous infections of any kind. Early sample harvesting for microbiological diagnosis, radical surgical debridement and in-travenous antifungal therapy are crucial for eradication of mucormycosis and patient recovery.Funding statementNone of the authors (TM, KS, AT, SM) received any specific funding for this work.Consent for publicationThe patient and his relatives gave written and verbal consent to submission of this case report for publication. Written consent canbe presented on request.Declaration of Competing InterestNone of the authors (TM, KS, AT, SM) state any conflicts of interest.T. Maleitzke, et al. Trauma Case Reports 23 (2019) 1002214References[1] K. Hoffmann, J. Pawlowska, G. Walther, M. Wrzosek, G.S. de Hoog, G.L. Benny, P.M. Kirk, K. Voigt, The family structure of the Mucorales: a synoptic revisionbased on comprehensive multigene-genealogies, Persoonia 30 (2013) 57–76.[2] A. Katragkou, T.J. Walsh, E. Roilides, Why is mucormycosis more difficult to cure than more common mycoses? Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin.Microbiol. Infect. Dis. 20 (Suppl. 6) (2014) 74–81.[3] F. Lanternier, E. Dannaoui, G. Morizot, C. Elie, D. Garcia-Hermoso, M. Huerre, D. Bitar, F. Dromer, O. Lortholary, French Mycosis Study G, A global analysis ofmucormycosis in France: the RetroZygo study (2005-2007), Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 54 (Suppl. 1) (2012) S35–S43.[4] N.F. Jones, E.K. Shin, S. Eo, T.E. Starzl, Successful salvage of mucormycosis infection of the forearm and osteomyelitis of the ulna, Hand 3 (4) (2008) 332–336.[5] R. Verma, V. Nair, B. Vasudevan, P. Vijendran, V. Behera, S. Neema, Rare case of primary cutaneous mucormycosis of the hand caused by Rhizopus microsporusin an immunocompetent patient, Int. J. Dermatol. 53 (1) (2014) 66–69.[6] Kelpin J, Fahrenkopf M, Kelley J, Eichhorn M, Martin M. Mucormycosis osteomyelitis of the hand. J. Hand Surg. 2018.[7] B.J. Gardiner, I. Simpson, M.H. Khuu, S.E. Kidd, C.H. Lo, G.A. Jenkin, An unusual ulcer: a case of cutaneous mucormycosis caused by Rhizopus oryzae, Med.Mycol. Case Rep. 7 (2015) 8–11.[8] A. Skiada, F. Lanternier, A.H. Groll, L. Pagano, S. Zimmerli, R. Herbrecht, O. Lortholary, G.L. Petrikkos, European Conference on Infections in L. Diagnosis andtreatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3),Haematologica 98 (4) (2013) 492–504.[9] S. Sagar, S. Kumar, A. Gupta, M. Singhal, B. Mishra, Successful management of a case of primary cutaneous mucormycosis in an immunocompetent host, WoundsCompend. Clin. Res. Pract. 25 (5) (2013) 136–140.[10] H. Tempfer, A. Traweger, Tendon vasculature in health and disease, Front. Physiol. 6 (2015) 330.[11] C. Lidor, J.A. Nunley, Images in clinical medicine. Mucormycosis of the hand and forearm, N. Engl. J. Med. 337 (21) (1997) 1511.[12] J. Moreira, F. Ridolfi, R. Almeida-Paes, A. Varon, C.C. Lamas, Cutaneous mucormycosis in advanced HIV disease, Braz. J. Infect. Dis. Off. Publ. Braz. Soc. Infect.Dis. 20 (6) (2016) 637–640.[13] G. Petrikkos, A. Skiada, H. Sambatakou, A. Toskas, G. Vaiopoulos, M. Giannopoulou, N. Katsilambros, Mucormycosis: ten-year experience at a tertiary-carecenter in Greece, Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol. 22 (12) (2003) 753–756.T. Maleitzke, et al. Trauma Case Reports 23 (2019) 1002215

A case report of cutaneous mucormycosis of the hand after minor trauma in a patient with acute myeloid leukaemia

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A case report of cutaneous mucormycosis of the hand after minor trauma in a patient with acute myeloid leukaemia

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