The patient was a 64-year-old female. She was admitted because of fever and cough for 1 week. She had suffered from hypertension for more than ten years. She had been diagnosed with SLE 10 months previously because after developing a rash, which was mainly distributed in the skin, neck and both upper limbs. Meanwhile, laboratory tests showed positive results for anti-DS-DNA and anti-SSA antibody spectra. She was further diagnosed with membranous lupus nephritis based on pathological findings of renal puncture 7 months ago prior to admission. Her medications included methylprednisolone 24 mg once daily, cyclosporine 50 mg twice daily and hydroxychloroquine 0.2g twice daily, amlodipine 5mg once daily, febuxostat 40 mg once daily combined with a sodium bicarbonate tablet 0.5g three times a day, warfarin tablets 2.5mg once daily, torasemide 10mg once daily, potassium chloride 0.5 g once-daily. After treatment at a local hospital, the rash subsided. However, the urine protein of the patient remained positive, with an elevated erythrocyte sedimentation rate and hypoproteinaemia, and the patient therefore remained on immunosuppressive therapy.
A physical examination revealed a weak state. Her temperature was 36.4 C on admission (maximum temperature 38.5 C), her heart rate was 85 beats/min, her respiratory rate was 18/min, and her blood pressure was 140/76 mmHg. No obvious dry or wet rales were noted in either lung by auscultation. Laboratory data showed a white blood cell count of 6360/mm3, with 92.6% polymorphonuclear cells, 4.9% lymphocytes, and 2.1% monocytes. Platelets (34*109/L) were significantly decreased. Serum complement C3 (0.69g/L) and serum albumin (23.5 g/L) were reduced. Ur Prot/UrCreat (6.51g/g) was significantly elevated. The result of anti-DS-DNA result was negative, but anti-SSA antibody spectra were weakly positive (1:32). CD3+ (348*106/L), CD4+ (168*106/L) and CD8+ (180*106/L) lymphocyte subsets had a significantly decreased. In addition, the patient tested negative for human immunodeficiency virus (HIV).
The chest CT showed pneumonia in both lungs (Figure 1A). The patient was diagnosed with pneumonia, and received treatment with sulfamethoxazole and cefuroxime. The patient's body temperature fluctuated between 36 C and 38 C during hospitalization, and her pulmonary infection did not improve. It is necessary to exclude pulmonary tuberculosis and pneumocystis jiroveci pneumonia (PJP). Sputum for gram stain, culture and acid-fast smear was obtained. Culture of the sputum generated abundant normal oropharyngeal flora and Candida tropicalis. In addition, blood cultures were negative.
The patient remained febrile, with a temperature as high as 39.1 C. A repeat chest CT also showed further infection in both lungs compared with that at admission (Figure 1B). A bronchoscopy with BAL was performed. Purulent secretions were observed and a sample was taken from the left upper lung. A large amount of mould was also isolated in large amounts from the BAL fluid. BAL fluid stained with Gram, fluorescence and hexamine silver stains showed the presence of somewhat dichotomously branching septate fungal hyphae (Figure 2A-C). The GM results in the BAL and serum were 1.85 mug/L and 0.89 mug/L, respectively. According to the latest guidelines for invasive fungi, the GM results indicated the presence of fungal infection. Sulfamethoxazole and cefuroxime were discontinued and a new regimen of micafungin (150mg/d) and ganciclovir was initiated. The patient began to defervesce but the repeat chest CT also showed further infection in both lungs (Figure 1C). The patient died 10 days later. No autopsy was performed.
The purulent secretions were cultured on Sabouraud dextrose agar (SDA) (Emmon's modification) and on SDA with chloramphenicol at 28 C.The fungus grew at 28 C on SDA and on SDA with chloramphenicol. No growth was observed on Mycosel agar. Fungal morphology stained with Medan lactate showed a branching mycelium. Conidial terrier grew from the side ends of hyphae and formed a short broom at the top. The stem of the bottle was in the shape of a bottle. The conidia were spherical or elliptic (3-6 mum in diameter) (Figure 2D). The organism had white-coloured villiform and produced a slight yellow pigment on the reverse side, showing that had the most pronounced growth at 5 days on potato dextrose agar (Figure 2E). Notably, the organism developed a purple pigment on the reverse side after 14 days of growth on potato dextrose agar (Figure 2F). Attempts to identify the fungus were unsuccessful by morphology and the MALDI-TOF-MS system. The isolate was identified by sequencing using primers (ITS1: 5'-TCCGTAGGTGAACCTGCGG-3'; ITS4: 5'-TCCTCCGCTTATTGATATGC-3'). The mould was later identified as P. janthinellum by its DNA sequence. Antibiotic susceptibility testing was performed using a microdilution technique (CLSI M38-A2) (Clinical and Laboratory Standards Institute, 2008). Antibiotic susceptibility profiles showed that this strain had higher minimum inhibitory concentrations (MIC) values in response to many antifungal drugs (Table 1).
The chest CT showed nodules and patches in the upper lobe of the left lung on admission.