Deep Fungal Infections of the Upper Extremity - A Review

INTRODUCTION

Upper extremity infection is usually caused by bacteria, such as Staphylococcus and Streptococcus species.¹ Fungal infections are relatively rare, however there is an increasing incidence in recent years, due to the propagation of medical immunosuppression and the rise of the number of immunodeficient patients.²

Fungal infections of the upper extremity can be divided in three groups based on the depth of the infection, namely cutaneous, subcutaneous and deep. Cutaneous infections are located on nails and skin and are mainly caused by microorganisms that metabolize keratin. Subcutaneous infections affect the deep skin layers, subdermal fat, dermal nerves and blood and lymphatic vessels and bursae in the space overlying joints and are usually caused by low virulence organisms. Deep infections affect deep vessels and nerves, the synovium, tendons, muscles, bones and joints and are commonly caused by microorganisms that enter the body as spores and attack deep tissues of the upper limb in a different form.³ The latter are related to significant morbidity and mortality, varied from stiffness and contracture to the need of amputation and even death. This is because of the relatively usual delay in the diagnosis, and it is important in cases of immunosuppressed patients or deep infections resistant to conventional treatment, a fungal causing factor to be considered.⁴

The aim of this review is to collect information about all deep fungal infections of the hand reported in literature and give an update with emphasis on their presentation, diagnosis and treatment.

ASPERGILLOSIS

Aspergillosis is an infection caused by the Aspergillus fungal genus. Fungi can affect deep tissues by two ways, either as a regional expansion of primary cutaneous aspergillosis, or as a secondary location of disseminated invasive aspergillosis of other organs.² Deep infection has been described in both pediatric and adult population. Predisposing factors include malignant hematological disease, immunodeficiency after organ transplant, intravenous catheter placement, chronic granulomatous disease, burns and puncture wounds. Cosgarea et al described a case of a 42-year-old farmer with invasive aspergillosis after a metal spike injury, without any other morbidity factor.⁵ Clinical presentation varies from local swelling and restricted range of motion to deep necrotic ulcers and gangrene. In most cases empiric antibiotic therapy was given based on signs and symptoms, even though specific bacteria were not always isolated. Osteomyelitis, arthritis, myofasciitis, gangrene and deep diffused infections are the reported manifestations of deep aspergillosis. Four species have been isolated from biopsy specimen of involved tissue, A. flavus, A. fumigatu, A. niger and A. ustus. Co-infection with mucorales and phycomycetes species have been detected. Diagnosis is based on microscopic morphology, histopathological examination and culture result. Aspergillus reveals characteristic fungal hyphae on potassium hydroxide wet preparation.¹ X-rays are helpful in cases of arthritis, osteomyelitis and in lung infiltrate detection in disseminated invasive disease and magnetic resonance imaging (MRI) is used for the diagnosis of myofaciitis and osteomyelitis. Treatment strategies mainly include surgical debridement and intravenous amphotericin B administration. Combination of amphotericin B with capsofungin and terbinafine, as well as switch of amphotericin B to oral fluconazole or itraconazole have been successfully tried. In advanced cases amputation may be inevitable. Klein et al. reported a case of a 52-year-old heart transplant recipient man with progressive gangrene of his fingers, caused by Aspergillus and mucorales species co-infection, who ended up in hand disarticulation.⁶ The cases of aspergillosis are presented on Table 1.

BLASTOMYCOSIS

Blastomycosis is a fungal infection caused by Blastomyces dermatitides. In most cases it sets up as pulmonary disease and it disseminates secondarily to deep tissues.¹⁴ Alternatively, deep infection is a result of regional spread of primary cutaneous blastomycosis, usually after contact with contaminated soil.^1,2 It has been described in pediatric and adult population, immunocompromised or not and it has been associated with history of pulmonary disease, diabetes mellitus, intravenous catheter insertion and local trauma. Banerjee et al. reported a 42-year-old diabetic man with hand blastomycotic osteomyelitis after an intravenous line infiltration.¹⁵Upper extremity deep infection may appear as verrucous ulcerative superficial lesion, subcutaneous nodules or articular swelling and restricted range of motion, while local x-rays demonstrate cortical defects and bone erosions. In addition, chest x-ray or computed tomography (CT) may show lung infiltrates. Osteomyelitis and septic arthritis are the deep demonstrations of systemic blastomycosis. Osteomyelitis of long bones is located at the epiphysis or subarticular region and from there it may spread to the joint and cause arthritis.¹⁶ Diagnosis is based on clinical signs, imaging, histopathological studies and cultures. Microscopy after periodic acid-schif or silver stains illustrate characteristic double refractile cell wall and broad-based buds.² Blastomyces dermatitides antigens are available, but they do not have the desirable specificity.¹⁶ Irrigation and debridement or lesion excision and antifungal therapy with amphotericin B or itraconazole were effective in most cases. Ketoconazole and fluconazole have also been used. Meier and Beekmann recommend itraconazole 200 to 400 mg/d or ketoconazole 400 to 800 mg/d for 6 months for mild infections and iv amphotericin B 0.4 to 0.6 mg/kg/d in total dose of 1.5 to 2 g for life threatening disease.¹⁷ The cases of blastomycosis are presented on Table 2.

CANDIDIASIS

Candidiasis is an infection caused by Candida genus. Invasion of deep tissues is less common than cutaneous and subcutaneous forms and it usually happens in immunosuppressed population. Patients with history of HIV or HBV infection, diabetes mellitus, rheumatoid arthritis, steroidal use, autoimmune hepatitis and Buckley’s immunodeficiency have been reported. In diabetic patients glycosylated proteins favor adhesion of Candida to epithelium.²³ However, deep candidiasis has appeared after trauma, burn injury, former surgical intervention and prolonged antibiotic therapy in immunodeficient patients. Clinical examination commonly reveals swelling and limited range of motion or a nontender mass, depending on the underlying infected tissue. Flexor and extensor tenosynovitis, pyomyositis, arthritis, periprosthetic infection and osteomyelitis have been reported. Dunkley and Leslie reported a rare case of candida prosthetic infection after silicone metacarpophalangeal arthroplasty in a patient with rheumatoid arthritis.²⁴ X-rays, MRI and technetium bone scan are used in the evaluation, but the final diagnosis is established by aspiration fluid or debrided tissue biopsy, histopathological examination and cultures.² C. albicans, C. glabrata, C. guilliermondii and C. parapsilosis have been isolated from fungal cultures. In direct microscopy Candida albicans has characteristic spherical budding yeastlike cells.²⁵ Treatment is corresponding to the infected tissue type and usually combines surgical intervention and antifungal agents. The former include surgical debridement, implant removal, synovectomy or amputation in advanced cases. Systemic antifungal therapy is based on fluconazole or amphotericin B administration.² However, other antifungal agents have also been used. Fichadiaa and Layman reported a case of flexor tenosynovitis from C. parapsilosis treated successfully with synovectomy, intravenous micafungin for 2 weeks and oral voriconazole for another 6 weeks.²⁶ Finally, Yang et al. recommend anidulafungin (a semisynthetic echinocandin) and fluconazole for 6 weeks for treatment of C. albicans pyomyositis.²⁷ The cases of candidiasis are presented on Table 3.

COCCIDIOMYCOSIS

Coccidiomycosis is an infection caused by coccidioides species, namely C. immitis and C. posadasii.¹⁵ Fungals found in the soil of endemic areas, such as United States, Mexico and South America. Their evolution relates to animal hosts, however transmission from animals to humans is rare.⁴ Disseminated coccidiomycosis affects both healthy and immunosuppressed hosts. In the later population it can be fatal in rare cases.³⁷ Acute lymphoblastic leukemia, Crohn’s disease, organ transplant, lymphocytic lymphoma, rheumatoid arthritis, juvenile inflammatory arthritis and diabetes mellitus are reported predisposing factors. Typically, patients have a history of pulmonary infection, presented with flu-like symptoms, which spreads secondarily to other sites, like the synovium, tendons, bones and joints of the upper extremity.³ Gropper et al. reported a case of coccidioidal flexor tenosynovitis in a 50-year-old man with acute lymphoblastic leukemia under immunossupressants and history of lung coccidiomycosis.³⁸ Upper extremity infection often presents as painful erythematous swelling or palpable mass with restricted rang of joint or finger motion. The most common manifestations are osteomyelitis, arthritis and tenosynovitis. The later can lead to tendon rupture. Also, Gavrin end Peterfy described a rare case of coccidioidal intramuscular cyst in the extensor muscles of his elbow.³⁹ Bone prominences at the insertion points of tendons and ligaments frequently are affected by coccidioidal osteomyelitis. There is also a predilection for sites such as humeral condyles, olecranon and radial and ulnar styloid process, where higher volume of red marrow is observed.¹⁷ Another interesting point is the rather frequent symmetric bilateral development.³⁷ X-rays demonstrate cystic and lytic lesions and in cases of articular involvement, loose bodies from subchondral bone can be seen.¹⁷ Microscopic evaluation demonstrates characteristic hyphae and immature spherules with endospores after periodic acid–Schiff (PAS) and silver methenamine stains.¹⁵ Cultures and coccidioidal complement fixation establish the diagnosis.¹ Tenosynovectomy is the treatment of choice for tenosynovitis; however, recurrence up to 50% has been reported.⁴⁰ Debridement and lesion excision are effective in other types of infection. Antifungals like amphotericin B, fluconazole and itraconazole are necessary and useful as additional therapy. Meier and Beekmann recommend itraconazole 400 mg/d or fluconazole 400 mg/d as first line treatment and ketoconazole 400 mg/d, secondarily, for 12 months or until 6 months after clinical improvement for mild infections and iv amphotericin B 0.5 to 0.7 mg/kg/d for 10 to 12 weeks followed by oral azole for more than a year for life threatening disease.¹⁸ The cases of coccidiomycosis are presented on Table 4.

CRYPTOMYCOSIS

Cryptomycosis is a fungal infection caused by Cryptococcus genus. It is associated with pigeons and pigeon droppings and host’s immunosuppression.² Deep infection has been described in patients with rheumatoid arthritis, diabetes mellitus, unicentric Castleman’s disease, Waldenstrom macroglobulinemia and after local trauma. Amirtharajah and Lattanza point out the importance of cryptococcal hand infection diagnosis in patients under TNF-a antagonist drugs.⁴ Superficial hand infections are a secondary manifestation of pulmonary involvement in most cases,³ while deep infections present as primary lesions. Usual presentation includes swelling and a tender mass of wrist or fingers with restricted motion. Flexor or extensor tenosynovitis is the most common diagnosis. Braun et al. reported an uncommon case of cryptococcal fistula infection in a diabetic patient.⁴⁵ Additionally, Chen et al. described a case of middle finger osteomyelitis from C. neoformans.⁴⁶ Microscopy detects characteristic ovoid budding yeastlike cells and thick capsules with India ink preparation.²⁵ Cultures also demonstrate numerous budding yeasts, and high cryptococcal antigen titer is the evidence of cryptococcal infection.³⁷ X-rays of osteomyelitis illustrate discrete osteolytic lesions with dense surrounding bone.¹⁶ C. neoformans is usually associated with deep upper extremity cryptomycosis. Hunter-Ellul et al. described a rare case of extensor cryprtococcal tenosynovitis caused by C. luteolus.⁴⁷ Debridement and synovectomy or excision is usually necessary followed by systemic antifungal therapy. Singh et al. reported the use of amphotericin B, fluconazole or itraconazole with concurrent flucytosine in organ transplant patients with C. neoformans infection.⁴⁸ Meier and Beekmann recommend fluconazole 200 to 400 mg/d as first line treatment and itraconazole 400 mg/d, secondarily, for 3 to 6 months and iv amphotericin B 0.3 mg/kg/d plus flucytosine 37.5 mg/kg/6h for 6 weeks or amphotericin B 0.5 to 0.7 mg/kg/d for a total dose of 1.5 to 2.5 g for life threatening disease.¹⁷ The cases of cryptomycosis are presented on Table 5.

HISTOPLASMOSIS

Histoplasmosis is a fungal infection caused by Histoplasma genus. Two kinds have been described. Histoplasmosis is associated with cat and bat feces, it is endemic to some areas like Ohio and Mississippi river valleys and is caused by H. capsulatum.² African histoplasmosis is a result of H. duoboisii invasion and it is reported in some African countries.⁵¹ Candida and bacterial co-infections have been detected. Immunocompromise states like organ transplant under immunosuppressants, diabetes mellitus and steroidal use for Crohn’s disease, rheumatoid arthritis, Sjogren’s syndrome and asthma predispose hosts to deep histoplasmosis infection. However, it has been described in immunodeficient patients, too. Onwuasoigwe et al. reported a case of forearm African histoplasmosis in a patient without any predisposing factor.⁵² Deep hand infection may be primary or disseminated after pulmonary involvement.³⁷ Erythema and swelling with or without distal numbness is the usual presentation. Fungal tenosynovitis, carpal tunnel syndrome, myofasciitis, bone cyst and osteomyelitis are the reported manifestations. Care et al. reported an uncommon case of capitate’s bone cyst in a patient with history of carpal tunnel syndrome from H. capsulotum.⁵³ Hypercalcemia and elevated serum angiotensin-converting enzyme may be found in blood serum test.²⁵ Diagnosis is established by fungal serologic test for Histoplasma-yeast forms, complement fixation test, culture and the discovery of large round single-celled spores by microscopy after Grocott’s methenamine silver strain.¹ In cases of tenosynovitis or carpal tunnel syndrome the infected synovioum is red-brown and sometimes contains rice bodies.² X-rays may illustrate bone erosion or distruction in cases of osteomyelitis. Surgical debridement, excision or synovectomy is necessary, followed by systemic antifungal therapy, such as itraconazole, ketoconazole or iv amphotericin B. Meier and Beekmann recommend itraconazole 200 to4 00 mg/d as first line treatment and ketoconazole 400 mg/d or fluconazole 400 mg/d for 6 to 12 months for mild infections and iv amphotericin B 0.4 to 0.7 mg/kg/d in total dose of 1.5 to 2.5 g for life threatening disease.¹⁷ The cases of histoplasmosis are presented on Table 6.

MUCORMYCOSIS

Mucormycosis is an infection caused by Mucorales order fungi. Mucor, Rhizipus and Absidia species are responsible for deep upper extremity mucormycosis infections.¹ Al-Qattan and al-Mazrou described the natural history of untreated upper extremity mucormycosis. First, dermal plexuses are invaded resulting in superficial enlarging black eschars. Subsequently, the infection spreads to subcutaneous vessels, manifesting as bleeding from the ulcerated skin. Finally, major arteries appear thrombosis causing distal gangrene.⁶¹ Cutaneous infection usually develops at sites of trauma or peripheral vessel catheter insertion.² Immunocompromised patients may have history of organ transplant, diabetes mellitus, HIV, intravenous drug abuse or systemic steroid use. In diabetic patients ketone reductases result in high-glucose conditions more favorable for Rhizopus.²³ Scheffler et al. reported a case of hand mucormycosis in a premature neonatal under corticosteroid use for respiratory distress syndrome.⁶² In immunocompetent patients it appears after severe injuries or burns. Moran et al. reported a series of mucor species upper limb infection after motor vehicle and conveyor belt injuries.⁶³ Clinical presentation varies from edema and black skin discoloration to deep ulcers and extensive necrosis. In most cases, gangrene requiring amputation is the devastating outcome. Early diagnosis and intervention are of upmost importance. Computed tomography and magnetic resonance imaging scans are rarely used to reveal the depth of invasion³ and routine fungal cultures seldom grow the causing species.⁴ Diagnosis is based on histopathological examination. Microscopy, after potassium hydroxide strain of biopsy specimens, reveals characteristic 90^ο hyphae.¹ Histological examination after a hematoxylin-eosin or periodic acide Schiff staining may demonstrate invasive thrombosis of minor or major vessels, leading to necrosis.⁶⁴ Aggressive debridement of necrotic tissue in early stages followed by systematic antifungal medication is necessary to prevent further dissemination. Liposomal amphotericin B at dose of 5 to 10 mg/kg/d with or without posaconazole is used in aggressive cases.⁶³ Bohac et al. successfully treated a man who had hand mucormycosis and Staphylococcus co-infection, after a conveyor belt injury, with Maggot therapy.⁶⁵ Amputation in healthy borders is inevitable in advanced cases. Cases of mucormycosis infections are presented on Table 7.

MYCETOMA

Eumycetoma is a fungal infection of skin and subcutaneous tissues, which can extent to deep structures. Actinomycetoma is a different type of mycetoma, caused by bacteria.²⁵ The most common causative agent of eumycetoma is Madurella mycetomatis, while Pseudallescheria, Acremonium, and Leptosphaeria have also been identified.¹⁴ Often, fungus invades the skin and subcutaneous tissues through minor traumas and may remain inactive for many years. Deep infection is a result of local spread and may result in functional deficit, bone erosion and even death.⁷⁵ Clinical presentation typically reveals regional swelling with sinus tracts and x-rays, CT scans and MRI demonstrate bone destruction.¹⁴ Except for these illustrative techniques, ultrasonography, cytological, histopathological examination and cultures are usually used for the diagnosis.⁷⁵ Recommended treatment is a combination of debridement, excision or amputation and antifungal agents, such as ketoconazole 400 to 800 mg per day or itraconazole 200 to 400 mg per day for 6 months to 3 years.⁷⁶ Fluconazole, voriconazole and posaconazole have also been tested. The high recurrence rate is noteworthy.¹⁴ Three cases of deep upper extremity eumycetoma were found in database research. Altman et al. described a case of hand eumycetoma from C. albicans after prolonged antibiotic therapy for a multibacterial infection at the same site. Subcutaneous lesion with draining sinus was extended to third metacarpal bone and bone excision followed by oral fluconazole for 6 months led to complete cure.⁷⁵ Tomimori-Yamashita et al. also reported a case of hand mycetoma caused by Fusarium solani treated with oral ketoconazole, without any follow-up.⁷⁷ Finally, Cartwright et al. reported a case of hand mycetoma from Leptosphaeria tompkinsii.⁷⁸ It developed in the palm of a clothing manufacturer with no significant past medical history. It presented as palm swelling with multiple sinus tracts. X-rays, MRI and surgical exploration revealed no bone involvement. Treatment with oral itraconazole followed by oral voriconazole at dose of 200 mg twice daily at first and consequently 300 mg twice daily was unsuccessful, as symptoms insisted, and MRI illustrated carpal and metacarpal bone involvement at 12 months’ time.⁷⁸ Cases of mycetoma infections are presented on Table 8.

SPOROTRICHOSIS

Sporotrichosis is a chronic or subacute granulomatous infection considered to be caused by Sporothrix schenkii, a fungus found in tropical and temperate areas, growing in decaying vegetation, rose thorns, soil and hay. Main target infection group are people spending considerable time working outdoors, such as florists, farmers, laborers, carpenters, beekeepers and fishermen. Infection is initiated with either direct abrasion - penetration of patient dermis from contaminated materials and subcutaneous inoculation of the fungus or by fungus spores inhalation. Direct inoculation is the common way of infection. Sites involved are usually uncovered by clothes body parts, such as distal extremities, chest and fascial head. Four types of sporotrichosis have been described, lymphocutaneous, fixed cutaneous, extracutaneous (involving mucocutaneous) and disseminated, with the first being the most common.⁷⁹ Disseminated form usually occurs in patients with altered immunity such as chronic alcoholism, diabetes mellitus, myeloproliferative disorders or patients under immunosuppression medication such as transplant recipients and HIV infection. Deep tissue sporotrichosis occurs because of direct inoculation, spreading from upper tissue layers or hematogenous/lymphogenous spreading. Joints, bone, muscles, tendons, synovium and peripheral nerves have been reported to be involved. Usual findings of joint infection are pain and swelling over the joint, with decrease in range of motion and progressive destructive arthritis. Reduction of joint space, abnormality of articular margins, joint effusions and soft tissue swelling are often seen. Regarding the upper limbs, hand small joints, wrist and elbow are more likely to be infected and shoulders are usually spared. Periarticular bone infection is thought to be secondary to joint infection. Radiographic features of chronic joint sporotrichosis are calcifications within the joint (rather caused by periarticular bone fragmentation), periarticular osteoporosis and erosions and rarely bursa calcification. Differential diagnosis of an unspecified granulomatous tenosynovitis should include sporotrichosis as stated by Stratton et al.⁸⁰ and it may be introduced even with a tendon rupture following tenosynovitis.⁸¹ Sporotrichosis may be present with single peripheral mononeuropathy due to nerve compression such as carpal tunnel syndrome⁸⁰ as well as multiple peripheral mononeuropathies following reasons such as nerve compression, nerve direct infection and bystander effect of immune response to the infection after immunosuppression medication withdrawal.⁸² Diagnosis of deep tissue sporotrichosis includes plain radiographs, CT and MRI scans, fine needle aspiration or surgical discharge with histopathological examination (granulomatous disease with asteroid bodies present at approximately 40% of patients) and cultures of material obtained. Multiple cultures may be needed to reach the diagnosis. Additionally, Moeller et al. reported the use of ultrasonography for the evaluation of periarticular sporotrichosis.⁸³ Treatment options for sporotrichosis include local measures such as hyperthermia, azoles (ketoconazole, itraconazole and fluconazole), polyenes (amphotericin B) and allylamines (terbinafine). Deep tissue infection is best treated with systematic amphotericin B, alone or with surgical debridement, followed by long-standing suppressive therapy with itraconazole as stated by da Rosa et al.⁸⁴ Engle et al. also reported an over 90% response rate of mild osteoarticular sporotrichosis treated with oral itraconazole 100 to 200 mg daily for 3 to 6 months.⁸⁵ Cases of sporotrichosis infections are presented on Table 9.

UNUSUAL DEEP INFECTIONS

A case of shoulder basidiomycosis was reported by Kothari et al. presented as fungal myositis after a thorn pick injury in an 11-year-old girl. Ultrasonography and MRI were used for the evaluation of the diffuse non-tender shoulder swelling and microscopy of aseptate hyphae and smooth-walled zygospores with characteristic conjugation beaks after lactophenol cotton blue wet mount established the infection by Basidiobolus ranarum. Itraconazole 100 mg/d for 6 weeks led to symptom resolution with no recurrence.⁸⁸

Phaeohyphomycosis is an infection caused by dematiaceous fungi.³ Patients present with papules, nodules, ulcers or swelling with or without motion limitation.¹⁴ Biopsy reveals characteristic brown hyphae from yeast-like cells, hyphae, or pseudohyphae produced in diseased tissue.²⁵ Treatment includes surgical debridement with antifungal therapy, itraconazole or fluconazole for mild cases and amphotericin B for more severe.¹⁴ Two cases of phaeohyphomycosis were discovered. Li et al. reported a case of hand arthritis and osteomyelitis from Alternaria tenuissima after a rose thorn injury. Debridement followed by oral itraconazole 200 mg twice daily led to resolvement of symptoms.⁸⁹ Sorkin et al. described a case of hand extensor tenosynovitis from Phialophora verrucosa in a 77-year-old woman with autoimmune hepatitis after a wood splinter trauma, resulted in extensor digitorum communis tendon rupture. After surgical synovectomy, extensor carpi radialis longus tendon transfer and a course of itraconazole followed by voriconazole led to satisfactory outcome.⁹⁰

Three cases of deep upper extremity infection from Fusarium species were found, except for one described in mycetoma category. Two of them, reported by Rosanova et al., referred to children with extensive burn injuries and led to finger osteomyelitis. Both were treated by intravenous and oral voriconazole, but one of them required amputation.³⁵ Furthermore, a case of a 55-year-old also burned man infected by Fusarium solani at his forearm, reported by Goussous et al., needed below amputation, too.⁹¹

Keshtkar-Jahromi et al. described a case of synovial infection from Paecilomyces lilacinus. The patient presented with swelling at the third metacarpophalangeal joint of his hand. Diagnostic synovectomy and microbiological examination revealed the causing factor. Three-month course of voriconazole, which stopped due to side effects, finally led to treatment.⁹²

A case of hand extensor tenosynovitis in a renal transplant patient caused by Phoma species was reported by Everett et al. Synovectomy followed by histopathological examination and cultures revealed the unusual causative fungi. Treatment with iv amphotericin B followed by oral fluconazole was insufficient at first, leading to recurrence. However, debridement and higher dose of iv amphotericin B eventually resulted in resolution of symptoms.¹⁰

Phycomycetes, a polyphyletic fungal taxon, have been isolated from sites of deep burn-wound infections of upper extremities. Both Foley and Shuck⁹³ and Salisbury et al.⁷ reported such cases of phycomycosis, most of them requiring amputation as an ultimate solution.

Three cases of deep infection of the upper extremity by Scedosporium apiospermum were found out in literature. Schaenman et al. reported a case of necrotizing deep soft tissue infection on the dorsal aspect of the wrist and forearm of a woman with history of Behcet’s disease. Surgical debridement followed by voriconazole therapy successfully treated the infection.⁹⁴ Abrams et al. described a case of wrist fungal extensor and flexor tenosynovitis of a woman with rheumatoid arthritis treated with tumor necrosis factor inhibitor. Radical tenosynovectomy and voriconazole administration were not completely effective, leading to loss of hand function.⁹⁵ Finally, Kim et al reported a case of hand extensor tenosynovitis of a woman with history of diabetes mellitus. They highlight that the diagnosis was confirmed by DNA sequencing of Scedosporium apiospermum. Debridement and fluconazole therapy were successful in this case.⁹⁶ Cases of other unusual fungal infections are presented on Table 10.

CONCLUSION

In this review we summarized the basic characteristics of all deep fungal infections of the upper extremity found in literature. Information about the clinical presentation, diagnosis and treatment of each main category were separately analyzed. It is proved that these infections are causes of high morbidity and mortality, especially in immunosuppressed patients. Proper evaluation and high level of suspicion are needed to treat them without delay and prevent further expansion and functional deficiency.

Corresponding Author’s information

Panagiotis Christidis MD, MSc
Resident Doctor
Department of Orthopedic Surgery,
General Hospital of Katerini, 60100
Katerini, Greece
+30 6940 730227
panagiotischristidis13@gmail.com

FUNDING

No funding was received.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

ACKNOWLEDGEMENTS

The authors declare that they have none to acknowledge.

AUTHORS’ CONTRIBUTIONS

All authors made substantial contribution and reviewed the document carefully prior to submission. KD, TK, CP and IK designed and coordinated the study. All aforementioned authors along with TD and PC performed the authorship of initial draft. KD, TK, PC, TK, PK and SV significantly contributed to the linguistic formatting and correction of the manuscript, revised it critically for important intellectual content, and were responsible for final proof reading of the article.