Fig.1. Osteolytic lesion with sclerotic margins without rupture of the cortex, at the level of the base of the second phalange of the first finger of the left hand.

Complementary tests:

X-rays: osteolytic lesion with sclerotic margins that did not break the cortex, in the base of the second phalange of the first finger of the left hand, with an image compatible with bone sequestration.

Fig.2. Recovery phase and asymptomatic state with persistence of some lesions with residual osteolytic aspect.

Haemogram: leukocytes: 6.7 U/μl (4.6-10.2), neutrophils: 51.6% (37-80), ESR: 6 mm/hour (0-16) and C Reactive Protein (CRP): 7.3 mg/L (0-5). Haematocrit, haemoglobin and other parameters were within normal ranges.

The lesion was drained with debridement, and samples were taken and sent to microbiology for culture and antibiogram. Empirical treatment was established with gentamicin and cefazolin.

Result of the microbiological study: “Isolated microorganism: Candida parapsilosis, sensitive to amphotericin-B, fluorocytosine, fluconazole and itraconazole”.

Definitive diagnosis:

Osteomyelitis of the second phalange of the first finger of the left hand due to Candida parapsilosis in a non-immunodepressed patient.

The patient was studied by the Infectious Service of our hospital, verifying the absence of an immunosuppressed state. After receiving the culture and antibiogram results it was decided to start treatment with fluconazole at a dose of 200 mg per day spread over two intravenous doses of 100 mg, along with local dressing daily, for 15 days. The patient experienced clinical improvement with the suppuration stopping and the wound evolving favourably. At 15 days oral treatment was started consisting of a 50 mg tablet of fluconazole every 12 hours, and 1 month after her admission the discharge report was issued continuing with the oral treatment.

Later, at one month from discharge the culture was negative and she was passed on to the Rehabilitation Service of our hospital which reports a hyperextension and rigidity of the left thumb at the level of the interphalangeal joint without any movement towards the flexion, with the scar adhered to deep planes which prevents the movement, with swelling and hypersensitivity in the scar zone. Rehabilitation Service recommended active assisted mobilization of the trapeziometacarpal, interphalangeal and metacarpophalangeal joints of the thumb, with circular massage in the scar, with percussion and in zigzag.

A month later the asymptomatic state of the patient was clear, although we observed a slight limitation of the function of the left thumb. An improvement in the radiographic image has been observed, although a lytic image persists in the control radiograph, and also CRP values at 0.57 mg/L (0-5) and an ESR of 4 mm/hour (0-16), which is due to she has been discharged by the Infectious Service after completing 4 months of antibiotic treatment and by the Orthopaedic Surgery and Traumatology Service, with the advice that if signs of the reactivation of the process such as fever, pain or suppuration are observed, she should re-consult.

Discussion :

Candida’s osteomyelitis is a rarely described entity, normally associated to a late manifestation of a disseminated candidiasis, this being more frequent in immunodepressed patients, where the clinical course is sometimes not controlled by amphotericin B.
In fact, Candida’s osteomyelitis has been described exceptionally in locations such as the zygomatic arch in a diabetic patient with oral candidiasis and possible direct inoculation3; or at vertebral level, where it is also not common4, and is very infrequent in the hand.
Also it has been noted after predisposing circumstances such as previous trauma, treatments with multiple antibiotics after surgery and non-lymphocytic leukaemia, in which case amphotericin B has been effective and it has been considered as an alternative to the use of other medications such as 5 fluorocytosine and/or ketoconazole.

Candida parapsilosis, in particular, is a fungus associated to endocarditis in patients addicted to drugs by the parenteral route, and is more and more considered as a nosocomial pathogen, with clinical manifestations such as fungaemia (up to 23% of cases, more frequent in men and with an 11% mortality)5, endocarditis, meningitis, endophthalmitis, septic arthritis and peritonitis associated to invasive intravascular procedures2, parenteral nutrition solutions, ophthalmic collyria and prosthesis6.

As far as arthritis is described they are normally monoarticular and sometimes located in the large joints, such as the knee, hip or shoulder, and related to arthroplasties, arthrocentesis etc. In a review, Weems found 8 cases of arthritis due to Candida parapsilosis but in no case did he see an infected hand1.
There are cases where the infection does not precede from a direct aggression of the joint as in the cases of addicts to drugs by the parenteral route. Candida has also been isolated in patients who were not addicted to drugs by the parenteral route; thus, a study by Cuende et al., identified 3 cases of septic arthritis: a case originating in a popliteal cyst infected by Candida albicans, a case in a patient with acute myelogenous leukaemia with arthritis of the knee and chemotherapy, and a case of oligoarthritis in a patient with a cardiac transplant7. It has also been found in the oropharynx of healthy neonates and in asymptomatic diabetics.

Candida parapsilosis has been identified as a frequent colonizing agent of the skin and particularly of the subungueal space, with a predilection for media that contain glucose solutions. The nosocomial acquisition of Candida parapsilosis has been considered with interest, for which 98 patient were studied in the ICU having presented evidence of the acquisition of Candida parapsilosis through direct contact by means of the hands of hospital personnel8. In fact, direct inoculation of the fungus has been more frequently seen in the case of Candida parapsilosis, with a better prognosis than in the case of disseminated candidiasis. Its predilection for vaginal or buccal epithelium, endothelial cells, fibrin clots or the inert surfaces of catheters or similar is emphasised. Candida’s osteomyelitis is sometimes associated to an infection of a postoperative wound with intense local pain.

The most reliable diagnosis is by fine needle aspiration puncture or open biopsy, also by later study by means of enzymatic restriction analysis (ERA) and the study of the chromosomal DNA.

With regard to infections of the hand, studies have been made on infections of the metacarpals and phalanges and the presence of fungal infections in 12% of the cases has been stated, Candida parapsilosis being exceptional.
The entry points for the infection are considered to be post-traumatic in 57% of cases, postoperative in 15% of cases, haematogenous in approximately 13%, contiguous infections in 9% of cases and 6% of cases of unidentified origin.
With regard to other agents, gram negatives have been stated in 15% of cases, mycobacteria in 3% and mixed infections in 35%. All of them would form 74% of positive isolations9. In the same way it is interesting to consider that infections of the phalanges or metacarpals by various agents have also been described such as:

- Mucormycosis, associated to a periungueal infection from local trauma, open fractures, burns, fractures or intramuscular injections, that require debridements, occasional biopsies and treatment with amphotericin-B10.
- Staphylococcus Aureus in patients with severe atopic dermatitis with infection of the distal phalanges, with swelling, erythema and pain in the fingers, and even with the isolation of Streptococcus viridans. Probably, skin already harmed by a dermatitis could be a field of culture, as opposed to smaller injuries of the fingers, to cause subungueal micro-abscesses of these agents which would affect underlying bone.
- Actinomycosis in metacarpals with the presence of sulphur-like granules, strictly anaerobic conditions of growth, and limitable with treatment with penicillin11.
- Tuberculosis at the level of the middle phalange of the hand. Mycobacterium marinum in fish and/or seafood handlers.
- Anaerobes, especially Bacteroides, Fusobacterium, Propionibacterium acnes, Clostridium from contiguous infection, bites, peripheral neuropathy, traumas etc. Also Prevotella and Porphyromonas from bites. Here it turns out especially useful to know that among the factors that most influence the development of osteomyelitis after a bite it is the delay of more than 24 hours in the debridement and the beginning of a suitable treatment.
- Salmonella, Coccidioides immitis, Varicella.

All of them would contribute to the wide aetiologic spectrum of osteomyelitis of the hand. In most of the cases the treatment is usually medical and surgical.

Candida parapsilosis would be treated with ketoconazole or its derivatives and always having 5 fluorocytosine or amphotericin-B as alternatives, also having certain control of the microorganism with allylamine SF86-327, chlorpromazine and difluoromethylornithine (DMFO)12.
As far as surgical treatment is concerned it is interesting to emphasize curettage of the area of the lesion, and even possible amputation, with a frequency of 39% in some studies9. Also other procedures have been used in cases of infection of the metatarsals such as the extensive debridement of the lesion, reconstruction using an external fixing and spacer with antibiotics and methyl methacrylate, following a bone graft13, and sometimes fixing the autologous iliac crest graft with a Herbert scaphoid screw 14. In other cases after curettage a plasty is made with the interossei muscles 15.

Conclusion:

Osteomyelitis of the hand requires a combined treatment, with antibiotherapy and various surgical procedures. The taking of samples at the beginning of the clinical picture or at the drainage of the injury can be crucial at the time of approaching this pathology. Candida parapsilosis’ osteomyelitis of the hand is exceptional and we must especially think about its appearance in cases of immunosuppression.

Reference :

1. Weems JJ Jr. Candida parapsilosis: epidemiology, pathogenicity, clinical manifestations, and antimicrobial susceptibility. Clin Infect Dis.1992 Mar;14(3):756-66.

2. Weems JJ Jr, Chamberland ME, Ward J, Willy M,
 Padhye AA, Solomon SL. Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers. J Clin Microbiol.1987 Jun;25(6):1029-32.

3. Arranz-Caso JA, Lopez-Pizarro VM, Gomez-Herruz P, Garcia-Altozano J, Martinez-Martinez J. Candida albicans osteomyelitis of the zygomatic bone. A distinctive case with a possible peculiar mechanism of infection and therapeutic failure with fluconazole. Diagn Microbiol Infect Dis.1996 Mar;24(3):161-4.

4. Menendez MA, Barberan J, Gomis M, Pastor JM. Vertebral osteomyelitis caused by Candida parapsilosis. Enferm Infecc Microbiol Clin.1994 Jun-Jul;12(6):316.

5. Herrero JA, Lumbreras C, Sanz F, Lizasoain M, Aguado JM, Pastor C, et al. Nosocomial fungemia caused by Candida parapsilosis. Enferm Infecc Microbiol Clin.1992 Nov;10(9):520-4.

6. Darouiche RO, Hamill RJ, Musher DM, Young EJ, Harris RL. Periprosthetic candidal infections following arthroplasty. Rev Infect Dis.1989 Jan-Feb;11(1):89-96.

7. Cuende E, Barbadillo C, E-Mazzucchelli R, Isasi C, Trujillo A, Andreu JL. Candida arthritis in adult patients who are not intravenous drug addicts: report of three cases and review of the literature. Semin Arthritis Rheum.1993 Feb;22(4):224-41.

8. Sanchez V, Vazquez JA, Barth-Jones D, Dembry L, Sobel JD, Zervos MJ. Nosocomial acquisition of Candida parapsilosis: an epidemiologic study. Am J Med.1993 Jun;94(6):577-82.

9. Reilly KE, Linz JC, Stern PJ, Giza E, Wyrick JD. Osteomyelitis of the tubular bones of the hand. J Hand Surg [Am].1997 Jul;22(4):644-9.

10. Stevanovic MV, Mirzayan R, Holtom PD, Schnall SB. Mucormycosis osteomyelitis in the hand. Orthopedics.1999 Apr;22(4):449-50.

11. Kargi E, Akduman D, Gungor E, Deren O, Albayrak L, Erdogan B. Primary extremity actinomycosis causing osteomyelitis of the hand. Plast Reconstr Surg.2003 Oct;112(5):1495-7.

12. Ryder NS. Specific inhibition of fungal sterol biosynthesis by SF 86-327, a new allylamine antimycotic agent. Antimicrob Agents Chemother.1985 Feb;27(2):252-6.

13. McFadden JA. Vascularized partial first metatarsal transfer for the treatment of phalangeal osteomyelitis. J Reconstr Microsurg.1998 Jul;14(5):309-12.

14. Proubasta IR, Itarte JP, Lamas CG, Majo JB. The spacer block technique in osteomyelitis of the phalangeal bones of the hand. Acta Orthop Belg.2004 Apr;70(2):162-5.

15. Kakinoki R, Ikeguchi R, Nakamura T. Second dorsal metacarpal artery muscle flap: an adjunct in the treatment of chronic phalangeal osteomyelitis. J Hand Surg [Am].2004 Jan;29(1):49-53.