Primary cutaneous nocardiosis of the head and neck in an immunocompetent patient

Background

Nocardia spp are aerobic gram-positive bacteria that are environmentally ubiquitous and belong to the actinomycetes group of bacteria.1 They typically cause opportunistic infections in immunocompromised patients although immunocompetent hosts may also be affected.2–5 There exists no internationally accepted classification scheme for nocardiosis to date, however, the clinical categories of pulmonary, disseminated and primary cutaneous nocardiosis are widely established. While the first two usually affect immunocompromised patients (eg, solid organ transplant recipients), primary cutaneous nocardiosis is typically an infection in immunocompetent hosts caused mainly by local trauma and subsequent environmental contamination.2–5 Nocardia brasiliensis is the species most frequently associated with cutaneous disease and mainly isolated in areas with tropical or subtropical climates.1 Clinical findings vary and cutaneous infection may present with cellulitis, abscesses, ulcerations, erythematous nodules or pyoderma. Thus, a clinical diagnosis of cutaneous nocardiosis is difficult, as it resembles other cutaneous bacterial infections (mainly Staphylococcus aureus, group A streptococcus), cutaneous fungal infections (such as sporotrichosis, cryptococcosis, histoplasmosis, blastomycosis or coccidiomycosis) and cutaneous parasitic infections (mainly leishmaniosis). Furthermore, infections caused by mycobacteria and cutaneous neoplastic disease have to be considered in the differential diagnosis. Moreover, diagnosis and treatment are often delayed due to the slow growth of nocardia in culture.6

Case presentation

A 50-year-old woman was referred to the University Hospital Zurich with a painful swelling of the right side of her face with extension to the neck, and an ulcerated plaque at her right temple. The patient returned from Greece the previous day and reported that she had been bitten by an unknown insect at the location of the plaque approximately 5 days ago. Over the intervening days, she developed fever and noticed a painful swelling spreading from the insect bite to the ipsilateral eyelid and down to the neck. After consulting a physician in Greece, an antibiotic therapy was started with oral cefuroxime. As the fever and swelling persisted throughout the therapy, she presented with the symptoms to a primary care physician in Switzerland, who referred her to a local hospital with subsequent admission to the University Hospital Zurich, a tertiary care hospital, on the same day. The patient’s medical history was otherwise unremarkable.

On admission, physical examination revealed the presence of an ulcerated plaque, 3.5×3.5 cm in diameter, with little purulent secretion at her right temple. The surrounding soft tissue showed inflammation, with painful erythematous swelling without induration, extending to the ipsilateral periorbital region and down to the neck (figure 1). Vital signs were: heart rate 88 bpm, blood pressure 125/77 mm Hg, temperature 37.6°C and peripheral oxygen saturation 94% without supplemental oxygen. Cranial nerve function was intact, and oral inspection was unremarkable.

Figure 1

(A) and (B) Initial presentation with right-sided swelling of the face and an ulcerated plaque at the temple. (C) Two weeks after initial admission.

Initial laboratory investigations showed a white cell count of 14.26×10⁹/L (reference range: 3.0–9.6×10⁹/L) and a C-reactive protein level of 138 mg/L (reference range: <5 mg/L). Additionally, a slightly elevated alanine transaminase of 45 U/L (reference range: <35 U/L) and gamma-glutamyltransferase of 103 U/L (reference range: 35–105 U/L) were detected.

A contrast-enhanced CT of the head and neck demonstrated diffuse reticulation of subcutaneous fat in the area of the right cheek and temple with subcutaneous and superficial soft-tissue swelling reaching the periorbital and preauricular region (figure 2). There were no radiological signs of major abscess formation, bone infiltration, vascular infiltration or cerebral venous sinus thrombosis.

Figure 2

(A) and (B) Contrast-enhanced CT scan showing diffuse reticulation of subcutaneous fat in the area of the right cheek and temple with subcutaneous and superficial soft-tissue swelling reaching the periorbital and preauricular region.

Blood cultures were obtained and wound swabs were taken from the ulcerated plaque for microbiological examination. An antibiotic treatment was started with vancomycin and cefepime. This regimen was chosen due to the reportedly high prevalence of drug-resistant bacteria in Greece, such as methicillin-resistant S. aureus and other multidrug-resistant bacteria.7 A biopsy of the ulcerated plaque revealed considerable inflammation with abscess formation indicating an underlying infection. Microbiological examination of aspirated pus and blood cultures remained negative. Screening for HIV was negative using a fourth-generation ELISA, as was screening for syphilis using a Treponema pallidum particle agglutination assay. Broad spectrum bacterial (16S rRNA gene) PCRs of initial wound swabs were negative, as were specific PCRs for Franciscella tularensis and Leishmania spp. After 8 days of incubation, gram-positive rods were detected in the microbial culture of the initial wound swab, leading to change of antibiotic therapy to intravenous amoxicillin/clavulanic acid. The isolate was identified as Nocardia spp by partial 16S rRNA gene sequencing. However, the exact species could not be identified as the sequence information did not allow for differentiation between N. brasiliensis and N. vulneris. Histopathology of the skin biopsy using Brown Brenn staining identified a thin and branching structure consistent with Nocardia spp (figure 3). Antibiotic therapy was changed to intravenous trimethoprim/sulfamethoxazole (TMP/SMX) at a dosage of 400 mg TMP every 8 hours. Susceptibility testing using ETEST (bioMérieux SA, France) revealed that the isolate was susceptible to TMP/SMX8 (minimum inhibition concentration (MIC)=0.64 mg/L) and amoxicillin/clavulanic acid9 (MIC=0.75 mg/L), intermediate to minocycline8 (MIC=2.0 mg/L) and resistant to cefepime9 (MIC=12.0 mg/L). Regular wound irrigation and consequent antibiotic therapy led to substantial clinical improvement and normalisation of C-reactive protein (CRP). After 17 days, the patient was discharged from the hospital and antibiotic treatment was modified to TMP 160 mg/SMX 800 mg, two tablets three times per day.

Figure 3

Histopathology of the skin biopsy using Brown Brenn staining shows a thin and filamentous structure consistent with Nocardia spp.

Outcome and follow-up

Initial follow-up was performed 6 days after hospital discharge. The patient stated that the day prior to the follow-up appointment a non-pruritic rash had started to develop on her arms and chest. She denied any other symptoms. At presentation, vital signs were normal and physical examination revealed a symmetric, erythematous maculopapular rash on the chest and arms sparing the palms and mucous membranes. Laboratory workup demonstrated mild lymphopenia of 0.6×10⁹/L (reference range: 1.5–4.0×10⁹/L) and slightly elevated liver enzymes with alanine transaminase of 81 U/L (reference range: <35 U/L) and aspartate transaminase of 73 U/L (reference range: <35 U/L). Based on the clinical course and a change of antibiotic therapy to TMP/SMX 13 days prior to the onset of the rash, we suspected a cutaneous drug eruption due to TMP/SMX, indicating a mild delayed-type hypersensitivity reaction. The patient was treated with oral antihistamines until resolution of pruritus and antibiotic treatment was changed to amoxicillin/clavulanic acid 875/125 mg three times per day to complete a total antibiotic treatment duration of 3 months. Close follow-up was conducted by the family doctor with resolution of the erythematous rash and normalisation of haemogram and liver enzymes. After a total of 3 months of antibiotic therapy, complete resolution of the skin lesion was observed.