Unusual sojourn of not-so-unusual pathogens.

In our day-to-day clinical practice, we are likely to come across a condition where the diagnosis of a patient is challenging. We are not supposed to be an ideal diagnostician, but our main responsibility lies in elucidating human problems in an empathetic manner. Therefore, it becomes highly imperative that any clinical situation is approached keeping in mind the unique individuality of a patient. Data gathered from history given by the patient and meticulous record of signs is of utmost importance. Even a trivial-looking sign may be of substantial help in diagnosis of a patient through hypothetico-deductive model of reasoning.[1]

Let us look at the illnesses that are great masqueraders. Tuberculosis, malaria, human immunodeficiency virus (HIV), fungal pathogens, malignancy, and pulmonary embolism fit perfectly well into this category. In this respect, some atypical organisms and fungal illnesses are of particular importance as they can lead to sub-acute to chronic and at times difficult-to-diagnose presentations. Aspergillosis, candidaisis, histoplasmosis, mucormycosis, and cryptococcosis are some of the examples of fungal illnesses. Most of these organisms are ubiquitous in nature and their pathogenesis depends on various host-related factors such as immunocompromised state.[2]

Both innate and adaptive immune responses come into action when an organism is introduced to an epithelial surface. Intact epithelia are able to curtail initiation of most of the infections, and therefore, it is considered as the first-line defense. Immediate reactivity is then followed by more specific adaptive responses that lead to destruction of intruder or development of different types of a particular illness.[34]

Inhaled fungi are responsible for a spectrum of infectious, allergic, and hypersensitivity disorders including allergic bronchopulmonary aspergillosis (ABPA) and hypersensitivity pneumonitis.[5] Environmental factors are also instrumental in the growth and propagation of fungi which can have an effect on the dose of pathogenic organism to which a person is likely to be exposed.[6] A mixture of all these factors is perhaps responsible for varied clinical presentations of illnesses caused by some atypical bacterial and fungal agents.

This issue of Lung India contains interesting papers on unusual presentations of some not-so-unfamiliar pathogens – actinomycosis, cryptococcosis, and aspergillosis.

The article by Chawla et al. describes a 70-year-old female patient presenting with massive hemoptysis of short duration resembling tuberculosis and a mass-like endobronchial lesion similar to lung carcinoma.[7]

Her chest X-ray showed right upper-zone consolidation with signs of pleural effusion. Bronchial washings and biopsy were unremarkable, while fine needle aspiration cytology (FNAC) and trucut biopsy of the lesion helped in diagnosis of actinomycosis.

Actinomycosis is a bacterial illness that is mainly responsible for subacute to chronic illness of cervicofacial and abdominal areas. Characteristic indurated lesions with fibrotic walls and sulfur granules are the pathognomonic features of the disease. Presentation of chest disease may take form of a pulmonary parenchymal or pleural disease. The cauliflower-like endobronchial lesion in the patient described by Chawla et al. led to its confusion with malignancy. Thoracic actinomycosis usually presents as pneumonia, pleural thickening, pleural effusion, or empyema.[8] Perhaps, it was involvement of right-main bronchus and consequent hemoptysis that led to a relatively early diagnosis of the disease in this patient.

Abruptness of symptoms in the patient described by Chawla et al. must not be mistaken as presence of an acute illness. Actinomycosis may not present clinically for months or even years after the initiation of infection. Common symptoms, if present, are weight loss, fever, and chest pain.[8]

Authors have rightly pointed out that actinomycosis is one of the most inappropriately diagnosed diseases of human beings. Time and again, even expert clinicians tend to misdiagnose the disease. This is due to its rarity, indolent nature of infection, and presence of features similar to various other common illnesses like tuberculosis and malignancy. Actinomycosis should be suspected if one of the following three types of presentations is encountered: (1) Mass-like lesion that is spreading across the tissue planes, (2) recurrent sinuses with sulfur granules, and (3) remitting and relapsing infection after the course of antibiotic.[8] Though, the authors have discussed about the ideal treatment regimens along with duration, duration of treatment for their patient was not mentioned.

The article by Panigrahi et al. is on pulmonary and central nervous system (CNS) cryptococcosis in an otherwise healthy and young person.[9] The authors were asked to evaluate a 36-year-old male who was found to be having a mass-like lesion on his chest radiograph. Computed tomography (CT) of chest revealed a large mass with central liquefaction. Development of headache after hospitalization of the patient led to a magnetic resonance imaging (MRI) scan of head which showed meningeal enhancement. Cerebrospinal fluid (CSF) analysis and endobronchial biopsy of mass lesion revealed the presence of cryptococcal organism. The patient responded to a combination of amphotericin B with flucytosine followed by fluconazole. The identification of species was not possible as the culture of CSF and blood for the fungus was negative. Genotyping is required currently for confirmation of species.[10]

There are two main pathogenic species of cryptococci, and as mentioned by the author, Cryptococcus gattii was the more likely pathogen in this case, as it predominantly causes CNS and pulmonary disease in immunocompetent individuals. Reason behind the infection involving a person with intact immune system is not clear, but it may be due to epidemiology of host and characteristics of infection.[11] Most laboratories do not differentiate between the species and label them as Cryptococcus neoformans.

C. gattii has a tendency to grow on eucalyptus trees and is endemic to parts of Papua New Guinea and Australia. It has been recognized as an emerging infection in some other parts of the world. Interestingly, genetic type of fungus, changing condition of climate, use of land, and susceptibility of host are some of the factors thought to be contributing to the spread of fungal infection in geographically disparate localities.[12]

Another interesting article is by Bhatnagar et al. on pleural aspergillosis.[13] Pleural aspergillosis has been reported infrequently in the standard scientific English literature. Some hypotheses regarding occurrence of pleural aspergillosis have been put forward in the past. Pleural aspergillosis may occur as a complication of underlying chronic pulmonary aspergillosis. The smoldering parenchymal infection that is typical of chronic pulmonary aspergillosis may reach the pleura directly or through a pre-existing fistula.[14]

Another hypothesis is that invasive pulmonary aspergillosis may lead to development of a bronchopleural fistula and subsequently aspergillus empyema.[15] The case described by Bhatnagar et al. had basically an aspergillus pyopneumothorax, and the authors should have tried to find out associated parenchymal abnormality. This could have been done with the help of a CT scan of thorax and an appropriate procedure confirming the diagnosis by histopathology.

Pleural aspergillosis usually occurs when there is some underlying structural lung abnormality. The explanation by authors regarding pleural aspergillosis occurring secondary to aspiration of material from dental carries is less convincing. Aspergillosis has not been known to occur due to microaspirations. On top of that, why would aspiration occur in a healthy person? Additionally, how can an aspirated material reach pleura without the presence of anatomical continuity such as a pleuro-pulmonary fistula? It would have been more helpful for readers to have a clear impression about illness if the author had also mentioned the course of adjunctive antibiotics and treatment other than antifungal agents and antitubercular drugs. Neither a CT scan of thorax nor a fungal culture of initial pleural aspirate was done.

Pleural aspergillosis in this patient was diagnosed many weeks after intercostal tube drainage (ICD). The portal of entry for aspergillus, therefore, could have been from skin at the drainage site. Among other organisms, Aspergillus species is frequently reported to be present in hospital environment.[1617] It is also cultured from sputum and skin of hospitalized patients.[1819]

Some tests are of great help in the diagnosis of invasive aspergillosis. The most important is presence of hyphal structures in the tissue. Sometimes, instead of hyphal structures, conidiophores (fruiting bodies) are found on histopathology of tissue specimens.[20]

For the reasons mentioned above, it is important to do a pleural biopsy in patients with pleural aspergillosis. Even if a CT scan is normal in a case of pleural effusion primarily due to aspergillosis, thoracoscopy may show signs of associated parenchymal involvement, such as a cavity.[21] Other tests like some antigen and serological tests are helpful in confirming the diagnosis.[22] Galactomannan antigen assay can be used as a prognostic test.

In conclusion, the above-mentioned presentations included in this issue of Lung India are some of the examples of diseases that are frequently misdiagnosed, underdiagnosed, or treated inappropriately. Fortunately, all the patients described above were diagnosed in time and managed suitably. In routine clinical practice, it is worthwhile to remember some unusual presentations caused by not-so-unusual organisms. Explanation of occurrence of pleural aspergillosis in the case described above was less undeniable for the reasons mentioned above. In the other case report, identification of cryptococcal species and genotyping would have led to a more confident diagnosis. These factors are highly imperative in order to be able to influence the psyche of readers of a scientific journal. Authors must recognize the need of more rigorous workup of cases, like tissue diagnosis, culture, and identification of species of an organism according to the current standards for publication in a journal.