Diagnosis Of Hypersensitivity Pneumonitis Research Articles

Multidisciplinary team approach on a case of bilateral interstitial pneumonia

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by exposure to a wide variety of organic particles. In this article, we report a rare case of a 44-year-old male patient with cough and shortness of breath for more than 4 years and exacerbation for 1 month. The findings of lung computed tomography (CT) and pathology supported a diagnosis of chronic HP. The patient had a history of ulcerative colitis for 5 years, and used to take salazosulfapyridine more than 4 years since 2013. We organized domestic and foreign experts to discuss the diagnosis and treatment of this case. The final clinical diagnosis was chronic interstitial pneumonia [related to sulfasalazine or inflammatory bowel disease (IBD) itself], pulmonary infections. It is recommended to discontinuation of sulfasalazine and oral administration of glucocorticoids and required long-term follow-up.

Hypersensitivity Pneumonitis High-resolution Computed Tomography Findings, and Their Correlation with the Etiology and the Disease Duration.

Hypersensitivity pneumonitis (HP) is an immune-mediated diffuse parenchymal lung disease induced by inhaled antigens. High-resolution computed tomography (HRCT) is widely used in the diagnosis and follow-up of patients and determining the progression and prognosis of the disease. In this retrospective study, 45 consecutive patients with the final diagnosis of HP, seen at a large tertiary care center during a period of 4 years, were included and their HRCT findings were evaluated. The most common HRCT findings were ground glass opacity and reticulation. Some HRCT patterns were detected more severely in bird fanciers in comparison with other etiologies. There is no "gold standard" for the diagnosis of HP. HRCT findings play an important role in hypersensitivity pneumonitis diagnosis and CT scan also help to define the severity of hypersensitivity pneumonitis injuries. In our study, reticulation and ground glass opacity were the most common findings in HRCT of patients with HP. We also find that patients with avian contacts had a significantly higher rate of fibrosis.

Acute hypersensitivity pneumonitis in woodworkers caused by inhalation of birch dust contaminated with Pantoea agglomerans and Microbacterium barkeri.

Five workers (2 males and 3 females) employed in a furniture factory located in eastern Poland developed hypersensitivity pneumonitis (HP) after the pine wood used for furniture production was replaced by birch wood. All of them reported onset of respiratory and general symptoms (cough, shortness of breath, general malaise) after inhalation exposure to birch dust, showed crackles at auscultation, ground-glass attenuations in HRCT examination, and lymphocytosis in the BAL examination. The diagnosis of acute HP was set in 4 persons and the diagnosis of subacute HP in one. Samples of birch wood associated with evoking disease symptoms were subjected to microbiological analysis with the conventional and molecular methods. Two bacterial isolates were found to occur in large quantities (of the order 108 CFU/g) in examined samples: Gram-negative bacterium of the species Pantoea agglomerans and a non-filamentous Gram-positive actinobacterium of the species Microbacterium barkeri. In the test for inhibition of leukocyte migration, 4 out of 5 examined patients showed a positive reaction in the presence of P. agglomerans and 2 in the presence of M. barkeri. Only one person showed the presence of precipitins to P. agglomerans and none to M. barkeri. In the inhalation challenge, which is the most relevant allergological test in the HP diagnostics, all patients reacted positively to P. agglomerans and only one to M. barkeri. The results indicate that P. agglomerans developing in birch wood was the main agent causing HP in the workers exposed to the inhalation of dust from this wood, while the etiologic role of M. barkeri is probably secondary. The results demonstrate that apart from fungi and filamentous actinobacteria, regarded until recently as causative agents of HP in woodworkers, Gram-negative bacteria and non-filamentous actinobacteria may also elicit disease symptoms in the workers processing wood infected with large amounts of these microorganisms. The results obtained also seem to indicate that cellular-mediated reactions are more significant for causing disease symptoms compared to those that are precipitin-mediated.

Hypersensitivity Pneumonitis (Including Environmental Assessment): Diagnosis and Management

This article aims to provide an overview on the diagnosis and management of hypersensitivity pneumonitis (HP). We will focus on the issues surrounding the lack of an international consensus on the diagnosis of HP, and review the existing treatment options for HP. There is emerging international consensus that HP should be classified based on clinical, radiologic, and pathologic features and not solely on disease duration. Environmental assessment and antigen avoidance remains the most important step in managing HP. Antifibrotics may soon become a viable option for chronic HP in the near future. Well-designed prospective controlled studies are underway. Substantial gaps still remain in our understanding of the diagnosis and management of HP. Further research should focus on establishing internationally accepted diagnostic criteria and clinical practice guidelines to aid the clinician in the challenging treatment of patients with HP.

Usefulness of bronchoalveolar lavage in a French pediatric cohort with hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a rare interstitial lung disease in children, and very little data are available on the frequency, diagnosis, and outcomes of HP. In a pediatric cohort with HP, the characteristics of the CD4/CD8 lymphocyte ratio are often described as nonspecific. We used the National French Database (RespiRare) to collect data from the last decade on HP. The diagnosis of HP was defined by the presence of a relevant exposure, clinical symptoms, and compatible lung imaging radiology and was usually defined by positive precipitins antibodies. A total of 16 children with a mean age of 10 years (4-13) presented with HP. All children presented with dyspnea on exertion. Diffuse ground-glass opacity was present in all computed tomography (CT) scans. Research guided by a questionnaire and precipitins antibodies against the corresponding antigens showed that patients were positive for contact with birds with or without fungi. Bronchoalveolar lavage (BAL) was performed in 12 children. The total cell counts were elevated in BAL fluid, with a mean value of 36% lymphocytes. The CD4/CD8 lymphocyte ratio was below one for all children. BAL in our pediatric cohort with HP had the same characteristics as that of adults with HP. An HP diagnosis must be considered when dyspnea on exertion and diffuse ground-glass opacity are observed. Carrying out BAL and serological tests can help diagnose and avoid lung biopsy.

ATTACK OF THE FOAMY MACS: DIFFUSE PANBRONCHIOLITIS IN A CAUCASIAN WOMAN

SESSION TITLE: Pulmonary Pathology II SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/21/2019 3:15 PM - 4:15 PM INTRODUCTION: Diffuse Panbronchiolitis (DPB) is a rare condition most commonly seen in patients of Asian descent (1). We identified a Caucasian patient with alpha-1antitrypsin (α1AT) MS genotype, who was diagnosed with DPB after multi-disciplinary discussion (MDD). CASE PRESENTATION: A 41 y/o woman with a diagnosis of hypersensitivity pneumonitis (HP) was referred for environmental exposure evaluation by an occupational/environmental pulmonologist to find the cause of her HP. She had presented five years previously with cough productive of yellow sputum. She reported a history of seasonal allergies. Her cough did not improve with bronchodilator use. Prednisone did provide some relief at a dose of 40 mg daily but was discontinued due to insomnia and edema. Her chest CT showed tubular bronchiectasis in both lower lobes and peribronchial thickening with peripheral infiltrates. Surgical lung biopsy demonstrated features thought to be consistent with HP. Comprehensive environmental exposure history was unrevealing. Physical exam revealed intermittent coughing, diffuse crackles and expiratory low-pitched wheezing. Due to discordance between her clinical & exposure history, chest imaging and pathology, her case was presented at MDD conference. During this MDD, thoracic radiology impression was that her imaging represented an airways-centered process such as bronchiolitis. Thoracic pathology review found bronchiolocentric lymphocytic infiltrations with germinal centers distributed in the middle of the secondary lobule, interstitial lymphocytes, and foamy macrophages in the interstitium, sparing the alveolar spaces. The massive lymphocytic infiltration in a bronchiolocentric pattern along with interstitial foamy macrophages was consistent with the unique pathologic pattern of DPB. Additional laboratory tests found normal α1AT level (125), but abnormal genotype (MS). CFTR gene sequencing and autoimmune antibodies were normal. CBC showed no leukocytosis or eosinophilia. She was treated with erythromycin and noted improvement in cough. DISCUSSION: DPB can be a rare cause of cough in non-Asian patients. α1AT MS genotype has been associated with airway disease and may be the reason for this patient’s presentation (2). Here, MDD yielded a refinement in clinical diagnosis, which led to alteration in care. Treatment for DPB includes chronic macrolide use, a therapy different from traditional therapies for HP, and would have not been instituted without this diagnostic refinement. CONCLUSIONS: This case highlights the utility of MDD approach in increasing diagnostic confidence of rare pulmonary diseases. Reference #1: Poletti V, et al. Diffuse panbronchiolitis. Eur Respir J 2006; 28:862. Reference #2: Sandford AJ, et al. Z and S mutations of the α1-antitrypsin gene and the risk of chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 1999; 20: 287–291. DISCLOSURES: No relevant relationships by Cheryl Augenstein, source=Web Response grant recipient relationship with Department of Defense, Department of Veterans Affairs, CDC Please note: >$100000 Added 03/18/2019 by Stella Hines, source=Web Response, value=Grant/Research Support No relevant relationships by Mary Richert, source=Web Response No relevant relationships by Bethany Weiler-Lisowski, source=Web Response No relevant relationships by Sarah Williams, source=Web Response

Histopathological spectrum of hypersensitivity pneumonitis with clinico-radiologic correlation.

There is no consensus on the classification of the diagnostic certainty of hypersensitivity pneumonitis (HP) based on the histopathological findings. This retrospective study aimed to describe the clinical and histopathological spectrum of HP. Herein, we also propose different grades of diagnostic certainty. Based on the histology, the cases were classified as: 'definite HP', 'probable HP', and 'possible HP'. Of the 47 subjects screened, 30 cases of histologically diagnosed HP (mean age 48.4years; 50% women) were included. The findings of cellular bronchiolitis, interstitial pneumonia, interstitial granuloma, isolated interstitial multinucleated giant cells (MNGCs), airspace granulomas, isolated airspace MNGCs, and organizing pneumonia were present in 96.7%, 80%, 46.7%, 50%, 10%, 63.3%, and 16.7% cases, respectively. Based on the various combinations of histopathological findings, the cases were classified as 'definite', 'probable', and 'possible' HP in 56.7%, 33.3%, and 10%, respectively. Chronic HP was diagnosed in 56.7% cases based on the presence of fibrosis on histopathology. The histopathological diagnosis of subacute or chronic HP did not corroborate with the disease duration, and 17.6% of the subjects with duration of symptoms of <6months had evidence of fibrotic disease on histopathology.

Pneumopathie d’hypersensibilité révélée par un syndrome de détresse respiratoire aiguë

Hypersensitivity pneumonitis (HP) are typically subacute in their presentation and the diagnosis may be difficult. We report a case of a hypersensitivity pneumonitis in a 27-years-old woman, caused by exposure to mould in an insalubrious mobile home. The initial presentation was with acute respiratory distress syndrome complicating RSV pneumonia, treated with ribavirin and corticosteroids in winter 2013-2014. The diagnosis of hypersensitivity pneumonitis was based on clinical and radiological relapse occurring during winter 2014-2015 with confirmed exposure to antigen with fungal sampling at home, respiratory deterioration with antigen rechallenge and a compatible chest CT-scan. The diagnosis of hypersensitivity pneumonitis should be considered in similar cases. Treatment is based mainly on removing exposure to the causative antigen.

Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis

Specific (s)IgG antibodies against environmental and occupational antigens, especially from bacteria, moulds, yeasts, birds and chemicals play an important role for hypersensitivity pneumonitis (HP). An increased serum level of sIgG is one criterion in the diagnostic procedure of HP and crucial for the detection of the triggering antigen for successful avoidance of further exposure. In contrast to specific IgE, sIgG concentrations in healthy individuals vary greatly depending on the antigen, which makes it difficult to differentiate from patients with HP. The aim of this study is to update or establish sIgG-reference values for important HP antigens in a healthy blood donor group. Therefore a study including six clinical centres in Germany was conducted to collect sera from 121 subjects without any signs of HP and without obvious exposure to potential HP antigens. Specific IgG to 32 typical HP antigens were quantified by ImmunoCAP (ThermoFisher Scientific; Phadia, Uppsala, Sweden). For validation selected measurements were repeated, total IgG was determined, sera were tested for unspecific binding with the human serum albumin ImmunoCAP Ro401, and influence of potential confounders was analysed. Statistical distribution of the antigen-specific IgG values was evaluated and the nonparametric method of percentile calculation was applied. The levels of IgG antibodies to the different antigens varied considerably in the study group from <0.02 to 726 mgA/L. Low sIgG levels were found against the chemicals and the highest levels to fungal antigens, especially to Aspergillus fumigatus and Botrytis cinerea. For three isocyanates, three acid anhydrides, Trichosporon pullulans and Acremonium kiliense reference values were proposed for the first time. For several avian antigens, moulds, and bacteria pre-existing reference values nearly could be confirmed without significant deviations, but already the 90% quantile for sIgG against Penicillium chrysogenum, Aspergillus fumigatus and pigeon antigen (Ge91) clearly exceeded the pre-existing values. In contrast, the 97.5% quantile value for Candida albicans was nearly half of the pre-existing cut-off value. In most cases specific IgG values were not significantly influenced by smoking and gender and most of them were unaffected by age. For implementation of these sIgG reference values into the routine diagnosis of HP, we provide an online available calculator to rank measured sIgG concentrations to the 32 different ImmunoCAP antigens.

Hypersensitivity pneumonitis recognised in a single pulmonary unit, between 2005 and 2015 - comparison with recently proposed diagnostic criteria.

Hypersensitivity pneumonitis (HP) is the third most common interstitial lung disease after idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Pathogenesis of HP is related to repeated exposure to inhaled environmental antigens that sensitise the susceptible, genetically predisposed persons. The aim of the present retrospective study was to summarise the diagnostic methods used in consecutive patients with HP, recognised in a single pulmonary unit, between 2005 and 2015, and to compare them with current diagnostic criteria. 135 patients, 68 males, 67 females, median age 53 years (18-75 years), entered the study. Chest CT features characteristic of HP were defined as: mosaic attenuation of lung parenchyma, air trapping and/or ill-defined centrilobular nodules. Lymphocytosis in BAL was defined as ≥ 30%. Median time from first symptoms to diagnosis was 12 months. The exposure to one or more allergens was found in 94% of patients, chest CT features characteristic of HP have been reported in 87%, BAL lymphocytosis - in 86%. According to recent diagnostic criteria - in 54% of patients, clinical diagnosis of HP was confident, in 16% - probable, in 26% - possible and in 4% - unlikely. The confirmation of HP with lung biopsy has been obtained in 36% of non-confident cases (16% of the study group). HP diagnosis was confirmed according to current diagnostic criteria in 70% of patients diagnosed between 2005 and 2015. Contradictions to lung biopsy have been the main reason for inability to confirm HP in non-confident cases.

Frequency of goose and duck down causation of hypersensitivity pneumonitis within an 80-patient cohort

BackgroundA variety of antigens have been identified as causative of hypersensitivity pneumonitis (HP), which is characterized by inflammation to the lung parenchyma that is induced by exposure. Goose and duck down (GDD) bedding is often overlooked by physicians as a potential cause, yet the use of GDD has markedly increased in recent years, paralleling an increased frequency of reports of GDD-induced HP. ObjectiveTo determine the frequency of GDD as the causative antigen in patients with HP who use bedding that contains GDD. MethodsPatients referred with a working diagnosis of HP underwent a detailed environmental history. Those who were using GDD were asked to remove it as an avoidance procedure. Signs, symptoms, spirometry, and inflammatory markers were followed up at weekly intervals for up to 1 month to determine the effect of remediation. ResultsEighty patients with HP were seen during an 8-year period. Thirty-two patients (40%) were using GDD bedding. Of these 32 patients, 12 (37.5% of those exposed and 15% of the total HP population experienced remission (or nonprogression) of disease by simply avoiding GDD bedding. Eleven (92%) of these 12 patients were female. In patients with GDD-induced HP, lung biopsy patterns were varied. ConclusionApproximately one-third of patients with HP, who slept with GDD, had persistent improvement or remission with simple avoidance. The higher incidence of GDD-induced HP in females may be hormonal and/or sociocultural related. Lung biopsy findings were across the spectrum of histopathologic patterns. Avoidance-challenge techniques were effective in confirming diagnoses and causation and mitigating the need for additional remediation.

Hypersensitivity Pneumonitis in Farmers: Improving Etiologic Diagnosis to Optimize Counselling

ABSTRACTIn a farmer, a diagnosis of hypersensitivity pneumonitis (HP) might cause drastic changes in life, and guidance concerning future prospects within farming requires a best possible etiological diagnosis. We aimed to assess (1) if immunological analyses based on material samples from the work environment could be used to improve the etiologic diagnosis in a farmer suffering from HP, and (2) if combining a longitudinal immunological investigation of workplace material with a realistic work place inhalation challenge could be used to optimize counselling with respect to further employment within farming. A realistic workplace inhalation challenge was performed to explore potential associations between exposure, symptoms and immune responses. Material samples were collected from various places on the farm, and enzyme-linked immunosorbent assay (ELISA) was performed to identify possible IgE and IgG antibodies in patient serum towards these material samples. Electrophoresis (SDS-PAGE) and immunoblot were used to detect the specific proteins in the material samples that were recognized by ELISA. The patient’s symptoms were reproduced by the workplace challenge, and more severe symptoms were associated with increased serum levels of specific IgG antibodies towards material samples from the workplace. The immunoblot detected IgG binding proteins in agreement with known allergens of the fungi Alternaria and Pullularia. Combining realistic workplace challenge with immunological analyses of workplace material may improve the basis for counselling farmers with farmer´s lung concerning future work within farming.

Hypersensitivity pneumonitis: Clinical manifestations - Prospective data from the interstitial lung disease-India registry.

Context:Multiple environmental factors are associated with development of hypersensitivity pneumonitis (HP), and diagnostic algorithms for the diagnosis of HP have been proposed in recent perspectives.Aims:We analyzed the data of patients with HP from interstitial lung disease (ILD)-India registry. The analysis was performed to (1) find the prevalence of HP, (2) reclassify HP as per a recently proposed classification criterion to assess the level of diagnostic certainty, and (3) identify the causative agents for HP.Setting and Designs:This was a prospective multicenter study of consecutive, consenting adult patients with new-onset ILD from 27 centers across India (March 2012–April 2015).Materials and Methods:The diagnoses were based on prespecified working clinical criteria and multidisciplinary discussions. To assess strength of diagnosis based on available clinical information, patients with HP were subclassified into definite HP, HP with high level of confidence, and HP with low level of confidence using a recent classification scheme.Results:Five hundred and thirteen of 1084 patients with new-onset ILD were clinically diagnosed with HP and subclassified as HP with high level of confidence (380, 74.1%), HP with low level of confidence (106, 20.7%), and definite HP (27, 5.3%). Exposures among patients with HP were birds (odds ratios [OR]: 3.52, P < 0.001), air-conditioners (OR: 2.23, P < 0.001), molds (OR: 1.79, P < 0.001), rural residence (OR: 1.64, P < 0.05), and air-coolers (OR: 1.45, P < 0.05).Conclusions:About 47.3% of patients with new-onset ILD in India were diagnosed with HP, the majority of whom were diagnosed as HP with a high level of confidence. The most common exposures were birds, cooling devices, and visible molds.

Pneumopathie d’hypersensibilité à mycobactéries atypiques se compliquant d’un abcès à Mycobacterium intracellulare

Mycobacteriumavium complex can be responsible for a number of different radio-clinical presentations, ranging from invasive infections to hypersensitivity pneumonitis due to repeated inhalation of antigens. The diagnosis of hypersensitivity pneumonitis is clinical, radiological, biological and microbiological. A 61-year-old male developed a hypersensitivity pneumonitis reaction to non-tuberculous mycobacteria, following the repeated use of his own spa, which later evolved into chronic respiratory failure. The diagnosis was made via an environmental analysis. Immunosuppressive treatment comprising corticosteroids and methotrexate led to moderate improvement, but may also have been responsible for the development of a M.intracellulare abscess. Despite 12 months of well-conducted antibiotic treatment, the evolution was unfavourable, with a relapse of a M.intracellulare infection three months after the end of treatment, followed by the patient's death. Hypersensitivity pneumonitis reaction to non-tuberculous mycobacteria should be considered in patients who have their own spa. In the absence of microbiological identification, environmental analysis may guide the diagnosis. A fatal evolution of PHS is infrequent but prognosis may depend on the degree of associated fibrosis.

Hypersensitivity pneumonitis: A fibrosing alveolitis produced by inhalation of diverse antigens

Hypersensitivity pneumonitis (HP) is a TH1 lymphocyte-biased fibrosing alveolitis caused by antigens ranging from avian excreta, fungi, thermophilic bacteria, and protozoa to reactive chemicals found in the workplace. Mimicking a viral syndrome, acute exposures to inciting antigens cause abrupt onset of nonproductive cough, dyspnea, and chills with arthralgias or malaise usually from 4 to 8hours later so that the temporal relationship between antigen exposure and symptoms might be unsuspected. The histology of HP reveals prominent lymphocyte infiltrates that thicken the alveolar septa with poorly formed granulomas or giant cells. Bronchoalveolar lavage fluid demonstrates greater than 20% lymphocytes in nearly all patients. Abnormalities on high-resolution computed tomographic examinations range from nodular centrilobular opacities in acute/subacute disease to increased reticular markings and honeycombing fibrosis, which typically are predominant in the upper lobes, in patients with advanced disease. Descriptors include "mosaic" attenuation and ground-glass opacities. Repeated episodes can result in nodular pulmonary infiltrates and suspected nonspecific interstitial pneumonia or idiopathic pulmonary fibrosis. Clinicians require a high level of suspicion to make an early diagnosis of HP before extensive pulmonary fibrosis or restrictive lung disease has occurred.

HYPERSENSITIVITY PNEUMONITIS DUE TO AN OUTDOOR ANTIGEN IN THE HOME

Introduction Common etiologies of hypersensitivity pneumonitis (HP) include avian, bacterial, fungal, occupational, and agricultural exposures. We present a case of HP to an external avian antigen that became present in the home. Case description A 69-year-old non-smoking retired teacher with adult-onset asthma presented with an 18-month history of dry cough without improvement with ICS/LABA or H2 antagonists. She had been treated with prednisone 10mg daily for four months with difficulty tapering due to cough. She denied fevers or weight loss. She had no pets although previously had a bird feeder in her yard but denied pigeon exposure. Exam was notable for diffuse rhonchi. Chest CT showed patchy ground glass densities. Spirometry demonstrated FEV1 1.70 (74%), FVC 2.41 (80%), FEV1/FVC 0.71. An initial HP panel was negative, but IgG sent later for pigeon droppings was positive. Due to high suspicion for HP, patient's home furnace filter was analyzed which showed a precipitin band to pigeon droppings. After changing home filters and avoiding pigeons, her cough resolved, and prednisone was tapered to 1mg. Discussion Organic material from pigeon droppings outdoors can become aerosolized and compromise indoor air quality. The diagnosis of chronic HP may be difficult to confer in patients with persistent asthma. Our patient's refractory cough, CT findings, serum IgG and filter pigeon precipitins, and symptom resolution with avoidance met criteria for HP. Despite not owning or working with birds and a negative commercial lab HP panel, a high suspicion allowed for identification of an unsuspecting outdoor source within the home.

Rare Presentation of Ceftriaxone-Induced Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a complex syndrome of varying intensity, clinical presentation and natural history rather than a single, uniform disease. Numerous inciting agents have been described including, but not limited to, agricultural dusts, bioaerosols, microorganisms (fungal, bacterial, or protozoal), and certain drugs. Prompt diagnosis of HP is important, as the disease is reversible when diagnosed early in its course. Correct diagnosis is based upon exposure history, clinical assessment, radiographic and physiologic findings, and, if possible, the response to avoidance of the suspected etiologic agent. J Med Cases. 2018;9(6):157-159 doi: https://doi.org/10.14740/jmc3046e

Stop Being So Sensitive: An Exceptionally Rare Report of Ustekinumab-Induced Sub-acute Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HSP) is a rare syndrome characterised by granulomatous inflammatory lung disease due to repeated sensitisation from a specific antigen. We present the case of a 61-year old male veteran with a history of nodular eczema who presented with 2 weeks of progressive dyspnoea on exertion and pleuritic chest pain. The patient was started on ustekinumab 5 weeks prior to presentation. Initial workup revealed ground-glass opacities on computed tomography (CT) scan of the chest. Cardiac workup was unrevealing with a normal myocardial perfusion stress test. The patient was started on inhaled corticosteroids and albuterol for reactive airway disease. Due to the persistence of symptoms despite treatment, the patient underwent bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy and endobronchial ultrasound-guided biopsy (EBUS). Bronchoscopy showed normal appearing airways of both right and left lungs. The BAL was remarkable for chronic inflammation and pulmonary macrophages. The BAL cell count differential was 1% granulocytes, 50% lymphocytes, 17% eosinophils and 32 mononuclear cells. The pathology from the mediastinal lymph nodes showed reactive inflammatory cells and no malignancy. The pathology from the transbronchial biopsy of the anterior basilar segment of the right lower lobe showed organising pneumonia with occasional ill-defined granulomas that stained negative for Acid Fast Bacilli (AFB) and Grocott's methenamine (GMS) appeared to be consistent with hypersensitivity pneumonitis. Based on the pathological diagnosis of HSP, the patient was managed with discontinuation of ustekinumab, with subsequent improvement of his symptoms. To our knowledge, this is the first report suggesting ustekinumab, like other biological therapies, has the potential to cause HSP.

Pathologic Separation of Chronic Hypersensitivity Pneumonitis From Fibrotic Connective Tissue Disease-associated Interstitial Lung Disease.

Chronic (fibrotic) hypersensitivity pneumonitis (HP) and fibrosing interstitial pneumonias associated with connective tissue disease (CTD-ILD) can be difficult to distinguish in biopsy specimens. To investigate features that might separate these entities, 2 pathologists blinded to the diagnoses reviewed 16 cases of chronic HP and 12 cases of CTD-ILD. Fifteen predefined parameters were examined by morphometric point counting, analysis/cm of lung tissue, or presence/absence. Germinal centers were present in a minority of patients, but favored a diagnosis of CTD-ILD (7/12 CTD vs. 2/16 HP; odds ratio, 9.80 [95% confidence interval, 1.50-63.4]; P=0.02). The number of lymphoid aggregates/cm (4.4±3.1 vs. 1.4±1.0; P=0.001), volume proportion of plasma cells (0.076±0.058 vs. 0.031±0.023; P=0.031), and plasma cell: lymphocyte ratio (1.03±0.71 vs. 0.35±0.22; P=0.001) were all significantly higher in CTD compared with HP. A diagnosis of HP was more common in the presence of peribronchiolar metaplasia (12/16 HP vs. 4/12 CTD; odds ratio, 6.00 [95% confidence interval, 1.15-31.2]; P=0.033) and in patients with a greater fraction of bronchioles showing peribronchiolar metaplasia (0.41±0.33 vs. 0.16±0.27; P<0.001). Number of fibroblast foci/cm, distribution of fibroblast foci, pattern of fibrosis, presence of giant cells/granulomas, and volume proportion of lymphocytes or eosinophils did not distinguish chronic HP from CTD-ILD. We conclude that no single morphologic measure definitively separates chronic HP from CTD-ILD lung biopsies, but numerous foci of peribronchiolar metaplasia favor HP, while the presence of germinal centers, large numbers of lymphoid aggregates, or a high plasma cell: lymphocyte ratio suggests CTD-ILD. Multidisciplinary discussion is often necessary for accurate classification inthis setting.

Utility of Circulating Antibody Serology in the Diagnosis of Hypersensitivity Pneumonitis

Utility of Circulating Antibody Serology in the Diagnosis of Hypersensitivity Pneumonitis