Summary
Skin nocardiosis is an uncommon form of cutaneous infection caused by Nocardia. More than 100 different species have been isolated and they mainly inhabit soil and water. Cutaneous affection can be divided into primary and secondary forms. Cell culture is the most used diagnosis method and trimethoprim-sulfamethoxazole the antibiotic treatment.We present a patient diagnosed with skin nocardiosis whose way of inoculation has not been described in the literature. However in future this kind of infection will probably increase due to the increasing interest in phytotherapy. Physicians should be aware of clinical manifestation, diagnosis and treatment.
Keywords: nocardiosis, burn, graft, debridement, aloe vera
Abstract
La nocardiose cutanée est une infection inhabituelle à Nocardia, dont il a été recensé plus de 100 espèces, d’habitat tellurique et hydrique. Les nocardioses cutanées peuvent être primaires ou secondaires. L’identification se fait en culture et le traitement classique est triméthoprime- sulfaméthoxazole. Nous présentons un cas de nocardiose cutanée secondaire d’origine inhabituelle. Ce type d’infection va probablement devenir plus fréquent en raison de l’intérêt croissant pour la phytothérapie si bien que les médecins devraient être avertis de ses manifestations clinique, du diagnostic et du traitement.
Introduction
The genus Nocardia belongs to the Nocardiaceae family which is defined as an aerobic filamentous gram-positive bacterium that can be transmitted by direct skin inoculation, inhalation or ingestion.1 These microorganisms are mainly found in soil, plants and water2 and they include more than 100 different species.3
Despite geographic distinctions, the most frequent species are Nocardia brasiliensis, Nocardia asteroides, Nocardia farcinica, Nocardia noca, Nocardia transvalensis, Nocardia abscessus and Nocardia cyriacigeorgica.3 Systemic forms of nocardiosis mainly affect immunosuppressed individuals; however, with regard to immune condition, localized forms are diagnosed without notable distinction. 4,5 Systemic outcomes frequently debut with sub-acute pulmonary affection that can develop into mediastinitis or pericarditis.6 Slowly and insidiously progressing abscess is the most frequent central nervous system affection. Therefore cranial MRI is recommended, especially in immunosuppressed people.6 Nocardiosis might also cause meningitis, endocarditis, peritonitis, keratitis, endophthalmitis, osteomyelitis or arthritis.1
As regards skin affection, the most frequently isolated species are Nocardia brasiliensis, Nocardia asteroides, Nocardia otitidiscaviarum and Nocardia farcinica. Cutaneous nocardiosis can be divided into primary (if direct skin inoculation) and secondary to systemic form. Trauma is the most common cause of primary cutaneous nocardiosis,7 which is subdivided into nocardial mycetome, localized cutaneous nocardiosis and lymphocutaneous nocardiosis.7 Differential diagnoses with Staphylococcus infection, sporotrichosis, ulceroglandular tularemia and Streptococcus infection2,8 should be taken into account.1,7
In recent decades there has been an increase in nocardiosis incidence, probably due to new immunosuppressant therapies to treat autoimmune diseases and new anti-rejection medicines in organ transplantation.3 Diagnosis is made by cell culture that can take up to two weeks. Trimethoprim-sulfamethoxazole is the most adequate treatment although it can be complemented with amikacine, cefotaxime, ceftriaxone or imipenem.9
Case report
A 69-year-old woman who suffered from dyslipidemia, psoriasis and atrial fibrillation presented to the Emergency Department of Vall d’Hebrón University Hospital Burn Unit for a seven-day scald burn on her right forearm. Physical examination suggested a soft tissue infection of the burn on the back of the right forearm (Fig. 1). The lesion presented spontaneous purulent drainage and the patient referred general malaise and fever up to 38ºC. Blood test showed leucocytosis (16.25 x 109/l) with 80.1% of neutrophils.
Fig. 1. Wound appearance at hospital admission.

The initial management was wound hygiene under regional anaesthesia. In order to complete diagnosis, a drainage liquid sample was sent for microbiological analysis. Topical mupirocin was used locally, intravenous piperacillin-tazobactam was started as empirical antibiotic and the patient was admitted to hospital. One day after admission, due to purulent drainage and fever persistence, the patient underwent surgical debridement (Fig. 2). Afterwards, hypochlorous acid and sodium hypochlorite liquid solutions (Microdacyn®) were applied every 8h to keep the wound bed clean. Two days after surgical intervention negative pressure therapy (NPT) provided by VAC system was begun (- 120 mmHg, continuous mode). It is noteworthy that after surgical debridement, fever ceased and the patient’s general condition improved.
Fig. 2. Surgical debridement.

Five days after the sample collection, microbiological results showed growth of Nocardia brasiliensis sensible to trimethoprim-sulfamethoxazole, therefore specific intravenous antibiotic therapy was started. Knowing the microbiological results, our team deepened the anamnesis and discovered that the patient had applied unprocessed aloe vera sap directly onto the burn during the first days after the accident, which might explain the source of the infection.
Granulation tissue grew after three days of NPT (Fig. 3) and split thickness skin graft obtained from the ipsilateral arm was used to cover the wound bed (Fig. 4). Two days after surgical intervention the graft was properly placed (Fig. 5), blood tests did not show alterations (leucocytes 9.77x109/L, 57.2% neutrophils) and general condition had improved, thus the patient was discharged from hospital.
Fig. 3. Wound bed preparation with NPT.

Fig. 4. Intraoperative skin graft.

Fig. 5. Wound appearance before hospital discharge.

One week (Fig. 6) and one month (Fig. 7) follow-up in outpatient clinics did not show any sign of recurrence and the skin graft was correctly inosculated. The patient was treated for four weeks with oral antibiotic without incidence.
Fig. 6. One-week follow-up.

Fig. 7. One-month follow-up.

Discussion
Primary cutaneous nocardiosis is an uncommon infection usually linked to skin trauma (contusion, wound or burn). In recent years, we have noticed a considerable rebound in phytotherapy, leading patients to improper uses of plants and herbs. This clinical case posed several diagnostic challenges: uncommon microorganism, complex microbiological identification and long-term microbiological results.10
Moreover, a bibliographic search on the Pubmed platform with the support of Medical Subject Heading (MESH) establishing the intersection of the key words “Nocardia” and “burns” yielded only one article in French reporting the clinical outcomes of a patient who acquired skin nocardiosis due to soil contact after falling from a two-wheel vehicle.11 No articles written in English have been found.
Primary skin nocardiosis is essentially caused by N. brasiliensis (80%), like in the case presented here. It typically occurs in individuals who suffer local trauma in contact with soil or plants.12 However, in the reported case the patient suffered a scald burn and the microorganism probably reached the injury because she had been applying unprocessed aloe vera to the burn. Increasing interest in phytotherapy in recent years leads us to believe that in the future these kind of infections could increase, therefore clinicians must be aware of the microorganisms that inhabit plants and soil.
Trimetoprim-sulfamethoxazol for 1 to 4 months is the treatment of choice.12 Due to slow growth in conventional culture, if there is no clinical suspicion of nocardiosis, the infection will be ineffectively treated with common empirical antibiotics, leading to the patient being subjected to aggressive surgical debridement, especially when systemic involvement is detected.
Nocardiosis should be considered when a skin infection does not respond to standard antibiotics and there is a precedent of plant or herb contact. Grau et al.13 emphasized the importance of exhaustive anamnesis in this kind of infection because the patient’s background could be essential to choosing optimal antibiotic treatment. It is also important to highlight the need to obtain a tissue or liquid drainage sample before starting antibiotic treatment. Clinically, skin nocardiosis should be considered when pustular lesions that progress to sporotricoid form appear. Cellulites, abscesses and ulcerations are also typical disease presentation forms.
Conclusion
Physicians should be aware of microorganisms that inhabit plants and soil because interest for phytotherapy has been increasing in recent years.
Anamnesis and tissue sample are two key points to achieving a correct diagnosis in soft tissue infections.
Complex and long-term microbiological identification could lead to the patient undergoing ineffective antibiotic treatment. Clinical appearance and background suspicion are fundamental to avoiding aggressive surgical debridement.
Acknowledgments
Funding.None.
Conflict of interest.The authors declare they do not have any conflict of interest.
Ethical approval.Not a requirement for case reports in our institution.
Informed consent.The patient consented to the procedure and the use of the images and photographs in this paper.
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