Cytologic diagnosis of pancreatic tuberculosis in immunocompetent and immunocompromised patients: a report of 2 cases

BACKGROUND: Pancreatic tuberculosis (PT) is a very rare occurrence in the setting of extrapulmonary tuberculosis. It usually occurs as a complication of miliary tuberculosis in immunodeficient individuals, particularly with HIV infections, but isolated involvement in an immunocompetent patient is extremely rare. Pancreatic involvement by tuberculosis in immunocompromised states, such as AIDS, and isolated involvement in immunocompetent patients require a high index of suspicion. Fine needle aspiration cytology under imaging guidance is highly conclusive. CASES: A patient presented with diabetes mellitus and a pancreatic mass clinically diagnosed as pancreatic carcinoma. A second patient, who was HIV seropositive, presented with generalized lymphadenopathy and a pancreatic mass, clinically diagnosed as lymphoma. These were conclusively diagnosed by fine needle aspiration cytology (FNAC) as PT under imaging guidance. After antituberculous therapy the first patient showed a dramatic improvement, whereas the second died; an autopsy was performed. Because of the atypical presentation of PT in immunocompromised and immunocompetent patients, FNAC can be used as a first-line diagnostic intervention. FNAC under imaging guidance is sensitive, specific, rapid and inexpensive. It resolves the diagnostic dilemma and thus avoids major surgery for a clinically diagnosed neoplasm.     

50例隐球菌血症的临床与预后分析

目的探讨不同免疫状态人群隐球菌血症的临床特点。方法对浙江大学医学院附属第一医院（2002年12月至2014年3月）50例隐球菌血症的临床资料进行回顾性分析,根据患者自身免疫情况分成免疫缺陷组（41例）和免疫健全组（9例）,对研究病例的性别、发病年龄、临床表现、实验室检查、抗真菌药物及疗效进行分析。结果 50例隐球菌血症中男性30例,女性20例,年龄15~83岁,平均（49±17.0）岁;43例有不同程度发热表现,性别、年龄、平均住院时间、临床表现、白细胞、中性粒细胞比例、C反应蛋白、尿素氮等在两组中差异无统计学意义,免疫缺陷组患者合并隐球菌性脑膜炎、同时合并隐球菌性脑膜炎及肺隐球菌病的病例高于免疫健全组。住院期间死亡10例,病情恶化13例,好转27例。结论隐球菌血症的临床表现不典型,免疫缺陷组较免疫健全组易引起隐球菌血症,免疫缺陷组更易合并隐球菌性脑膜炎及肺隐球菌病,隐球菌血症的预后差。     

The pathobiology of Aspergillus fumigatus

Aspergillus fumigatus is the most prevalent airborne fungal pathogen in developed countries, and in immunocompromised patients causes a usually fatal invasive aspergillosis (IA). Understanding the pathobiology of this fungal species requires not only analysis of the putative fungal virulence factors that stimulate fungal growth and/or survival in the lung environment, but also knowledge of the immune factors containing A. fumigatus in the immunocompetent host that can be debilitated by immunosuppressive therapies, triggering IA. Although the incidence of IA has dramatically increased in recent years, progress in these areas has been limited and, as yet, a single, true virulence factor has not been identified and the mechanisms responsible for protective immunity against A. fumigatus have yet to be elucidated.     

Rare and emerging agents of hyalohyphomycosis

The list of opportunistic agents of hyalohyphomycosis continues to grow, as does the number of immunocompromised patients; however, these mycoses also are manifested in patients who appear immunocompetent by current methods of detection. Although fungi causing hyalohyphomycosis span the Kingdom Fungi, the majority are found within the asexual or mitosporic fungi, with notable exceptions. The following is a discussion of recent, selected literature citations regarding hyaline fungi that are both “new” agents of disease, as well as “new” species within well-known taxonomic groups.     

Colitis por citomegalovirus en paciente anciano inmunocompetente

Gastrointestinal tract involvement due to cytomegalovirus infection is a condition that usually occurs in immunocompromised patients, but is uncommon in immunocompetent patients. In a review of 33 cases, the median age was 68 years, and the accompanying symptoms were diarrhoea (76%), abdominal pain (52%), and haematochezia, or melena (27%)^.The case is presented of ctyomegalovirus colitis in an 85 year-old man with no previously identified immunocompromised states.     

The Importance of a Proper Aetiological Diagnosis in the Management of Patients with Invasive Mycoses: A Case Report of a Brain Abscess by <Emphasis Type="Italic">Scedosporium apiospermum</Emphasis>

Scedosporium apiospermum is a saprobic fungus responsible for many different clinical manifestations. Although it affects mostly immunocompromised patients, pulmonary and disseminated scedosporiosis have also been reported in immunocompetent subjects. It often causes subcutaneous mycetoma, despite its preferential tropism to CNS. The authors describe a fatal case of a S. apiospermum brain abscess in a 58-year-old female. She was affected by chronic liver disease and idiopathic pulmonary fibrosis and had been treated with corticosteroid therapy for a long time. She recovered in a neurosurgery unit, wherein TC scan and cerebral MRI revealed an expansive left temporo-parietal process with vasogenic oedema. A stereotactic puncture of the lesion was carried out, and pus of brain abscess was evacuated. Empirical antifungal therapy was initiated with liposomal amphotericine B based on the clinical suspicion of Zygomycetes infection; after 3 days, posaconazole was added. The correct aetiological diagnosis arrived too late and the patient was treated with no specific therapy. This fatal case confirms the necessity of having a fast and correct aetiological diagnosis to improve the patient’s outcome.     

Asymptomatic pulmonary cryptococcosis diagnosed on fine needle aspiration cytology. A case report

BACKGROUND: Cryptococcosis can be a life-threatening mycosis in immunocompromised patients. However, it has a somewhat better prognosis in immunocompetent hosts. AIDS has led to an increase in the incidence of the disease. Clinically, the lesions can be confused easily with malignancy. CASE: A 25-year-old, asymptomatic male presented for a routine health check-up. The chest radiograph showed a subpleural left apical area of consolidation, suspicious for either a neoplasm or infection. Fine needle aspiration cytology (FNAC) revealed a granulomatous lesion with refractile yeast forms of Cryptococcus, both within the multinucleate giant cells and extracellularly. This was subsequently confirmed by culture and histology. CONCLUSION: The cytomorphology of cryptococcosis is characteristic, and FNAC is a useful modality for diagnosing the infection in asymptomatic patients but needs a high index of suspicion, especially in nonimmunocompromised patients.     

Subcutaneous Mycotic Cyst Caused by <Emphasis Type="Italic">Roussoella percutanea</Emphasis> in a UK Renal Transplant Patient

Fungi from more than 100 genera have been implicated in subcutaneous fungal infections, usually following traumatic inoculation of the etiologic agent. With the advent of molecular approaches to fungal identification and taxonomy, novel agents of subcutaneous mycoses are increasingly reported. In this manner, Roussoella percutanea, a novel species in Pleosporales, was described in 2014 from a subcutaneous mass in an immunocompetent male adult. Two additional cases involving renal transplant recipients were recently reported from patients resident in France and Germany, with several further cases discovered after analyses of historical culture collection isolates. Here, we describe a new case of subcutaneous R. percutanea infection, causing a mycotic cyst in a renal transplant patient resident in the UK. Although fungal infection was confirmed histologically, viable fungal isolates could not be recovered in culture from biopsy material and identification of the causative agent relied upon PCR amplification and sequencing of fungal rDNA genes. This is the fourth well-documented case of infection with R. percutanea in renal transplant patients, and the first reported from a patient resident in the UK. The current case illustrates the importance of molecular approaches for the identification of emerging fungal pathogens in culture-negative subcutaneous fungal infections.     

Meanderella rijsii,a new opportunist in the fungal order Pleosporales

Subcutaneous phaeohyphomycosis is an implantation disease caused by melanized fungi and affect both immunocompetent as well as immunocompromised individuals. Diagnosis and treatment require proper isolation and accurate identification of the causative pathogen. We isolated a novel fungus from a case of subcutaneous phaeohyphomycosis in an immunocompetent patient. The 56-year-old patient suffered from a slowly progressive swelling on the metatarsophalangeal join of the left food. The isolated fungus lacked sporulation and sequences of the ribosomal operon did not match with any known species. In a multi-locus phylogenetic analysis involving five markers, the fungus formed a unique lineage in the order Pleosporales, family Trematosphaeriaceae. A new genus, Meanderella and a new species, Meanderella rijsii are here proposed to accommodate the clinical isolate. Whole genome analysis of M. rijsii revealed a number of genes that can be linked to pathogenicity and virulence. Further studies are however needed to understand the role of each gene in the pathogenic process and to determine the origin of pathogenicity in the family of Trematosphaeriaceae.     

Experimental Pathogenicity of a Clinical Isolate of <Emphasis Type="Italic">Trichosporon dermatis</Emphasis> in a Murine Model

The pathogenicity of Trichosporon dermatis isolated from skin lesions of a patient has been examined in mice. Balb/c mice were treated with two intraperitoneal injections of 100 mg/kg cyclophosphamide on days 4 and 1 and one subcutaneous injection of 10 mg/kg dexamethasone on day 1 pre-inoculation, and then challenged with 0.2 ml T. dermatis inoculum (1 × 10⁸ CFU/ml) by topical application on an abrasive wound in the dermabrasive group and by hypodermic injection in the subcutaneous group. In the intravenous group, 0.2 ml of high (1 × 10⁸ CFU/ml) or low (1 × 10⁷ CFU/ml) inoculum was injected into the tail vein. Histopathology and inverse fungal culture were performed on the skin lesion and viscera, and renal fungal burden was also determined. Inoculated sites developed localized infections after dermabrasive and subcutaneous challenge in all mice, but the maximum area of skin lesions, and number of positive cultures from the lesions, were higher for immunocompromised mice. In the intravenous group, all immunocompetent animals survived during the four-week period, whereas 100 and 70% of immunocompromised animals died by 3 and 5 days in the high and low-inoculum groups, respectively. The incidence of disseminated infection and the renal fungal burden of immunocompromised mice were higher than those of immunocompetent mice. Our results demonstrate that subcutaneous and intravenous injection of T. dermatis can successfully establish cutaneous and systemic infection models in immunocompromised mice, with the kidney and lung being most susceptible.     

The role of IgG avidity determination in diagnosis of Epstein-Barr virus infection in immunocompetent and immunocompromised patients

There is a high degree of variability in the serologic response to Epstein-Barr virus (EBV) infection, especially in viral capsid antigen (VCA)-IgM antibodies. Therefore, additional tests are needed to confirm primary infection. We evaluated the value of IgG avidity determination in diagnosis of EBV infection in immunocompetent and immunocompromised patients. A total of 236 serum samples from immunocompetent patients with symptoms suggestive of EBV infection were tested for the presence of VCA-IgM/IgG antibodies and IgG avidity. Using IgG avidity, acute primary infection was confirmed in 56.7% of the immunocompetent patients with positive and in 1.8% of patients with negative VCA-IgM. Recent primary infection was documented in 8.9% of the IgM positive and 3.5% of the IgM negative patients. In patients with indeterminate serology (equivocal IgM), 6.7% were classified by avidity index (AI) as acute primary infection, 10.0% as post-acute and 83.3% as past infection cases. Concerning the 32 immunocompromised patients, recent primary infection was documented in 3 of the 14 IgM positive patients. High AI was detected in 11 of these patients, indicating an IgM response due to reactivation. Determination of IgG avidity in combination with classical serologic markers seems to be a reliable method to confirm primary infection both in immunocompetent and immunocompromised patients. It may be especially useful to differentiate cases of primary infection in patients with undetectable VCA-IgM antibodies or indeterminate routine EBV serology.     

Rare Fungal Infections in Children: An Updated Review of the Literature

An increasing trend of reports of rare fungal diseases has been observed to be mainly associated with the substantial increase of high-risk immunocompromised children, as well as with the selective pressure of antifungal drugs. On the other hand, recent reports have shown that several species of these rare fungi may also cause infections in immunocompetent children without obvious underlying conditions. The clinical spectrum of these infections, and most importantly their outcome, varies greatly, implying for a rather heterogenic group of pediatric infections. Various types of superficial and subcutaneous fungal infections, as well as systemic and disseminated life-threatening infections, have been reported. Prompt diagnosis and appropriate treatment of rare fungal diseases in children remains a great challenge. Several treatment options have been used, ranging from localized to combination treatment with extensive surgical excision and long-term antifungal therapy. We review contemporary data of rare fungal infections in pediatric patients focusing on epidemiology, mycology, management and outcome, published during the last three years.     

Primary Cutaneous Mucormycosis Caused by <Emphasis Type="Italic">Rhizomucor variabilis</Emphasis> in an Immunocompetent Patient

Primary cutaneous mucormycosis is an uncommon disease and occurs mainly in patients with immunocompromised disorders. We report a case of cutaneous mucormycosis in an immunocompetent man in whom no definite precipitating factors were noted. The isolate was identified as Rhizomucor variabilis according to the fungus morphology and DNA sequencing results. The lesion was successfully treated with oral Itraconazole, although the in vitro drug-susceptibility test showed resistance.     

Unusual Case of Cutaneous and Synovial Paecilomyces lilacinus Infection of Hand Successfully Treated with Voriconazole and Review of Published Literature

Paecilomyces lilacinus infection is rare and is found worldwide. The majority of infections occur in immunocompromised people. Among immunocompetent patients, cutaneous infections are the second most common site of infection but are difficult to treat because of antifungal resistance. We report a case of hand cutaneous involvement with synovitis in an immunocompetent patient that improved after treatment with oral voriconazole. To the best of our knowledge, there are only five published cases of cutaneous P.lilacinus infection, all in immunocompromised patient, treated with oral voriconazole. We review all previously reported cases.     

Listeriosis at Vancouver General Hospital, 1965-79.

The records were reviewed of all patients treated at the Vancouver General Hospital over the 15 years from 1965 through 1979 for infections proved by culture to have been caused by Listeria monocytogenes. Although listeriosis is not common in humans, certain groups seem to be susceptible - immunocompromised patients, pregnant women, neonates and the elderly. All these groups were represented among the 22 cases reviewed. There were 17 adults, 3 of whom were pregnant women who had only a mild influenza-like illness. Of the remaining 14 adults 9 were immunocompromised and 5 apparently immunocompetent; 7 presented with meningitis and 7 with bacteremia only. Of the five infants with neonatal listeriosis, two had early-onset disease (bacteremia) and three had the late-onset form (meningitis). Seven patients were treated with penicillin alone, seven with ampicillin alone and eight with penicillin or ampicillin combined with kanamycin, gentamicin or chloramphenicol. There were eight deaths: several were directly attributable to the listeriosis, but in others the severity of the underlying illness was an important factor. Serotypes 1 and 4b were equally common among the 16 specimens of L. monocytogenes that were typed.     

Tinea capitis in adults in southern Spain. A 17-year epidemiological study

BackgroundTinea capitis is an infection of the hair due to keratinophilic fungi, known as dermatophytes. Although the disease is common in children, several studies have also shown that it is far from unusual in adults, especially in post-menopausal women and immunocompromised persons.AimsTo determine the incidence of tinea capitis in adults in our area, as well as the predisposing factors (gender, immunity), and causative species.Materials and methodsA retrospective study was conducted over a period of 17 years, from 1995 to 2011, collecting data on cases of tinea capitis diagnosed in our dermatology department. Information collected for all patients included age, gender, location of the lesions, results of direct examination and culture, immune status, cause of immunosuppression, and the prescribed treatment.ResultsThirty-three cases (11.4%) out of 289 cases of tinea capitis occurred in adults. Most of these adults (72%) were immunocompetent, and the rest were immunocompromised for different reasons. Three of the patients were men and 30 women, with 70% of the latter being post-menopausal. Trichophyton species were isolated in 76% of these adult patients, with Trichophyton violaceum being the most common. Treatment with oral terbinafine was successful in all these cases. Microsporum species were responsible for the other cases, all treated successfully with oral griseofulvin.ConclusionsThis series of tinea capitis in adults is one of the largest to date. It shows that tinea capitis is not uncommon among the immunocompetent adult population. In our geographical area, except for prepubescent patients, most cases affecting the adult population were caused by species of the genus Trichophyton. In these cases the treatment of choice was oral terbinafine, which considerably shortened the treatment time, and was associated with fewer side effects than the classical griseofulvin.     

Cryptosporidium and cryptosporidiosis in Denmark--current status

The genus Cryptosporidium comprises a group of protozoan parasites that infect a broad variety of vertebrates causing severe diarrhoeal illness in immunocompromised as well as immunocompetent hosts. Although molecular heterogeneity of the genus is being increasingly recognised, traditional diagnostic methods do not discriminate all species/subtypes, and population genetic studies of these parasites, using discriminatory molecular markers, have only been published recently. In Denmark, Cryptosporidium research has focussed mainly on detection methods, pathogenicity and veterinary aspects. The present paper gives an overview of recent and ongoing Cryptosporidium research in Denmark with an emphasis on molecular approaches to study epidemiology and transmission.     

Recurrent bacteraemia caused by different Salmonella species in a systemic lupus erythematosus patient

Non-typhoidal Salmonella infections are increasingly being encountered. Recurrent systemic salmonellosis has previously been reported in both immunocompromised and immunocompetent hosts. However, recurrent salmonella bacteraemia by different species of salmonella has rarely been described. We report a patient with systemic lupus erythematosus having Salmonella enteritidis and Salmonella typhimurium infections after ingesting raw eggs and vegetables. Multiple internal organs, including left knee joint, left ovary and bones, were involved. The patient recovered with a prolonged course of antibiotics. This case illustrates that recurrent systemic salmonellosis can be caused by different species of pathogens, especially in immunocompromised hosts. Detailed food history and education on food hygiene is essential in making the diagnosis and preventing recurrence. A prolonged course of antibiotics may be needed to manage these cases.     

Immunosurveillance against tetraploidization-induced colon tumorigenesis

Circumstantial evidence suggests that colon carcinogenesis can ensue the transient tetraploidization of (pre-)malignant cells. In line with this notion, the tumor suppressors APC and TP53, both of which are frequently inactivated in colon cancer, inhibit tetraploidization in vitro and in vivo. Here, we show that—contrarily to their wild-type counterparts—Tp53^−/− colonocytes are susceptible to drug-induced or spontaneous tetraploidization in vitro. Colon organoids generated from tetraploid Tp53^−/− cells exhibit a close-to-normal morphology as compared to their diploid Tp53^−/− counterparts, yet the colonocytes constituting these organoids are characterized by an increased cell size and an elevated expression of the immunostimulatory protein calreticulin on the cell surface. The subcutaneous injection of tetraploid Tp53^−/− colon organoids led to the generation of proliferating tumors in immunodeficient, but not immunocompetent, mice. Thus, tetraploid Tp53^−/− colonocytes fail to survive in immunocompetent mice and develop neoplastic lesions in immunocompromised settings only. These results suggest that tetraploidy is particularly oncogenic in the context of deficient immunosurveillance.     

Acremonium strictum: Report of a Rare Emerging Agent of Cutaneous Hyalohyphomycosis with Review of Literatures

We present a case of cutaneous hyalohyphomycosis due to Acremonium strictum in an immunocompetent individual along with an overview of fungal infections caused by A. strictum. The diagnosis was confirmed by the presence of hyphae in microscopic examination of cutaneous biopsy and discharge, positive culture for A. strictum and sequencing of the isolate at reference centre. The infection resolved with itraconazole and terbinafine. Cutaneous or subcutaneous infections of A. strictum have rarely been reported. Fungemia or disseminated infection often with fatal outcome in immunocompromised patients was the most common presentation of A. strictum infection found in the literatures. The studies also reveal worldwide variation in the treatment regime and outcome of the treatment.