Penicillosis in Patient of Acute Kidney Injury with Adenocarcinoma Lung: A Rare Presentation

Copyright: © 2016 Narain U, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Introduction
Penicillosis is an invasive fungal infection that primarily occurs in the south east and eastern regions of Asia [1]. Penicillium species are among the most common fungi in the environment and are usually considered non-pathogenic to humans [2]. However in immunocompromised host they can be virulent pathogen and can cause death [3]. Acute kidney injury (AKI) is common in cancers [4] and patients on cytotoxic drugs are susceptible to opportunistic infections. Significant proportion of cancer patients are affected by pulmonary infections. Successful outcome requires early identification, aggressive and effective treatment of the infection. Herein, we report the case of successful treatment of concomitant pulmonary Penicillosis and acute kidney injury in the patient of adenocarcinoma lung.

Case Report
He was the diagnosed case of diabetes mellitus, hypertension, hypothyroidism and moderately differentiated adenocarcinoma lung. After completion of 16 th cycle of maintenance chemotherapy (Gemcitabine), he was readmitted with complains of fever, restlessness, cough, weakness, anemia, hypertension (180/90) and derranged kidney function. Next day he was referred to nephrology centre for further management. Before admission he was anemic, dyspnoeic, anuric, derranged renal function and was presenting with non-productive cough. On admission investigations revealed 100°F temperature, 86% S.PO 2 , 180/90 BP, 42/min RR, 140/min PR, S. urea 115 mg/dL, S. creatinine 4.43 mg/dL, S. Sodium 120 mmol/l, S. Potassium 41mmol/l. Urinalysis was not specific. Dysmorphic Red blood corpuscles were absent.
Chest examination revealed bilateral fine crepts and ronchi hence BIPAP support was given. Intravenous nitroglycerine started to control hypertension and antidiabitics, diuretics were added along with the conservative treatment of AKI. Various differential diagnosis in this setting was ruled out by appropriate investigations e.g. tumour lysis syndrome, contrast nephropathy, thrombotic thrombocytopenic purpura, obstructive uropathy and pre renal factors. X-ray ( Figure 1) showed bilateral non-homogeneous opacity in lower zones. We requested for Bronchoscopy ( Figure 2) on urgent basis and investigations were sent immediately to the lab. After stabilization Bronchoscopy was done and it revealed frothy, blood tinged, mucopurulent lavage. Bronchoscopist abandoned the procedure due to the seriousness of patient as SPO 2 was going down. Microscopy of Broncho alveolar lavage (BAL) revealed occasional gram positive

Abstract
Fungal infections are an increasing problem in immunocompromised patients. Members of the genus Penicillium rarely cause infections and are primarily limited to strains of the species Penicillium marnaffei. We are reporting a successfully treated case of culture proven pulmonary Penicillosis caused by Penicillium chrysogenum on the onset of Acute Kidney Injury in a patient of ademocarcinoma lung. cocci, conidia and hyphae like structures on gram staining. Lacto phenol cotton blue film confirmed the presence of fungal elements and acid fast bacilli were negative. On second day he had cough with streaky haemoptysis. Mantoux was negative. Urine and preliminary blood culture were sterile after 48 hours of incubation at 37°C. After third day sabourad dextrose agar showed tiny grayish green colonies of Penicillium chrysogenum ( Figure 3). On fifth day Hb was 7.5, Total Leukocyte Count (TLC) 13100 cells/cumm, with 88% neutrophils 12% lymphocytes, RBS 112, S. urea 104 mg/dL, S. creatinine 5.12 mg/dL, 2D Echo showed LV 55%, and kidneys were normal sized.  deteriorated and patient developed metabolic acidosis. Hence, he was put on haemodialysis for the indication of anuria. During dialysis five packs of packed red blood cells, three units of 100ml fresh frozen plasma and albumin were infused. Patient went into diuretic phase and most of the symptoms were resolved. After seven days of treatment, Hb was 10.4, 6100 cells/cumm TLC, 75% Neutophils, 25% lymphocytes 25.0, 80 mg/dl S. urea and creatnine 3.0 mg/dl. Kidney biopsy was done later on to get the exact histology against various differential diagnosis in cancer patient. According to biopsy tubules showed patchy areas of acute tubular necrosis, RBCs and WBC casts were seen in some tubules. Tubular atrophy comprised about 15-20% of cortex. Interstitium showed mild edema. Mild diffuse interstitial inflammation were seen comprising chiefly of eosinophils, few lymphocytes and plasma cells. Arteries and arterioles did not show any significant diagnostic abnormality. Direct Immunoflurosence showed 3-4 glomeruli which did not show staining for IgG, IgA, IgM, C3, C1q, Kappa and Lambda. Nonspecific trap noted for C3, C1q and focally for IgM. Therefore findings favour to Acute Tubular Necrosis (Figure 4).

Discussion
Alterations of the immune system in uremics constitute a complex issue. On one hand, hypercytokinemia is a typical feature of uremia, likely due to accumulation of pro-inflammatory cytokines as a consequence of decreased renal elimination and/or increased generation following induction by uremic toxins, oxidative stress, volume overload, comorbidities, etc. [5,6]. On the other hand, uremia is associated with immunosuppresion due to the impact of the uremic milieu and a variety of associated disorders exerted on immunocompetent cells. Hence uremia is associated with a state of immune dysfunction characterized by immunodepression that likely contributes to the high prevalence of infections [7]. The genus Penicillium is ubiquitous, generally saprophytic, and distributed worldwide [8]. However, some species are known for their positive or negative effects on humans. The positive impacts include their use in food fermentation and the production of drugs, and the negative effects are related to the production of Mycotoxins, the induction of hypersensitivity reactions (e.g. asthama and extrinsic allergic alveolitis) and infection of the humans [9]. Members of the genus Penicillium rarely cause infections and are primarily limited to strains of the species Penicillium marnaffei [10]. As reviewed by Lyratzopoulos et al. [11], only fifteen cases of invasive infections caused by species other than T. marneffei have been linked to the Penicillium genus worldwide. More recently, other Penicillium species, such as P. chrysogenum, P. piceum and P. purpurogenum, were found to be associated with these infections [12]. In the past, Penicillium chrysogenum has been recognized as an invasive fungus in only three cases of human disease [8,13]. Apart from toxins liberated by fungi, one of the specific pathogenic factors of Penicillium chrysogenum causing invasive infection is its ability to grow at 37°C [14] because majority of Penicillium species grow below 37°C; however, exceptions include P. citrinum, P. decumbens and P. janthinellum. In our opinion, both the Penicillium chrysogenum ability to grow at 37°C and patient's uremic state contributed for the development of fungal pneumonitis in the patient of adenocarcinoma lung. Pulmonary infections with fungi, including Penicillium species, are associated with much higher mortality rates in patients with nosocomial infections or infections complicating organ failure. Patients with Penicillium species infections have been treated successfully with itraconazole, amphotericin B, or fluconazole. However, some patients with conditions caused by Penicillium species have died despite treatment with ketoconazole, amphotericin B, or itraconazole [15]. That is why we gave combined therapy of Amphoterecin B and itraconazole in our case and finally we achieved successful outcome. This is the first study where we made a striking and novel observation of Penicillosis caused by Penicillium chrysogenum on the onset of Acute Kidney Injury in a patient of ademocarcinoma lung. The noteworthy observation is we diagnosed early and attained successful outcome with recovery of kidney function.

Conclusion
It concludes that if identified, diagnosed and treated promptly with the help of X-ray, bronchoscopy, direct microscopy of the specimen and supportive appropriate therapy patient may lead to better outcome which is relatively uncommon but not impossible.