Considerations and clinical management of infections in sarcoidosis.

PURPOSE OF REVIEW: To summarize data from recent reports about risks and outcomes of the infections most often reported in patients with sarcoidosis. RECENT FINDINGS: Rates of fungal infections and other severe infections are higher in patients with sarcoidosis compared to controls. Immunosuppression further increases the risk for an infection requiring hospitalization. In contrast, outcomes of coronavirus disease 2019 (COVID-19) are not worse unless lung impairment or other comorbidities are present. SUMMARY: Tuberculosis, fungal infections, and other severe infections requiring hospital admission are, fortunately, relatively rare in patients with sarcoidosis who live in nonendemic regions. However, ongoing vigilance is required when the course of sarcoidosis is atypical or inexplicably progressive, as costs are high when these infections are missed. In contrast, COVID-19 and other respiratory viral illnesses are common, including among patients with sarcoidosis. When organ impairment is minimal, an underlying diagnosis of sarcoidosis does not appear to increase the risk of severe COVID-19, but patients may have higher risks due to comorbidities, which are important factors to address in routine sarcoidosis care. The burden from respiratory viral events, including impacts on quality of life and life functionality including work capacity, is unknown and is important to measure.

Sarcoidosis and frailty: recognizing factors that foster holistic resilience.

PURPOSE OF REVIEW: Sarcoidosis is a multiorgan system disease exerting significant impact on biophysical, social, psychological and emotional well-being. Mortality and disability correlate to accessible, timely, expert care for sarcoidosis and its related complications. Across health conditions, positive healthcare interactions and interventions can rehabilitate unfavourable factors tied to concepts of ' frailty' . Here, we set out to introduce concepts related to frailty and their impact in the context of sarcoidosis. RECENT FINDINGS: Studies examining frailty across other multiorgan and single organ-based diseases that mirror organ involvement in sarcoidosis demonstrate findings that bear relevance in sarcoidosis. Namely, factors predisposing a person to frailty are a multifactorial phenomenon which are also reflected in the lived experience of sarcoidosis; and that early diagnosis, intervention and prevention may alter a course towards more favourable health outcomes. SUMMARY: Factors predisposing to frailty in other health conditions may also signal a risk in sarcoidosis. In turn, proactive health preservation - regardless of age - may lead to improved biopsychosocial reserve and health-related quality of life. Fortifying holistic resilience in sarcoidosis is anticipated to reduce risk of the occurrence and prolongation of health-related complications, and facilitate swifter recovery from biophysical complications as well as from psychosocial and emotional stressors.

Clinical utility of nailfold capillaroscopy.

Nailfold capillaroscopy (NFC) is a simple noninvasive microscopic technique used to identify characteristic morphological abnormalities in the nailfold capillaries. The presence of this microvasculopathy appears to be of fundamental importance in the pathological processes that underlie the scleroderma spectrum disorders (including dermatomyositis and antisynthetase myositis). This review discusses the different methodologies and techniques in performing NFC and stresses the diagnostic utility achieved with simple 'bedside' techniques utilising the ophthalmoscope, dermatoscope or smart phone. Recent advances in reporting abnormal microvascular patterns and vascular metrics (e.g. capillary density and dropout) are discussed. The aetiopathogenesis of the microvasculopathy is currently unknown but its close association with Raynaud Phenomena and specific autoantibodies together with recent observations from sequential NFC allows speculations on its possible mechanism. Finally, future developments in the use of NFC as a possible biomarker in the management of the scleroderma spectrum disorders are discussed, with a recommendation that NFC becomes more widely available, particularly in rheumatological, immunological and dermatological practice. NFC provides a clinically accessible window on the pathologic process fundamental to scleroderma-related disease.

Barriers and enablers to the family meal across time; a grounded theory study comparing South Australian parents' perspectives.

Family meals are positively associated with numerous beneficial health and social outcomes. Current discourse however claims that parents are faced with numerous barriers when trying to bring the family together to share a meal. Solutions for overcoming barriers to a positive shared family meal are often individualistic and do not address the systemic pressures and burdens families have faced for decades. The aim of this study was to explore the systemic and novel barriers and enablers to shared family meals as experienced by families across time. To achieve this, a qualitative study informed by grounded theory was conducted. Parents of South Australian families were recruited and interviewed in the 1990s, and a new sample of parents were recruited and interviewed in 2020. Transcripts were analysed using grounded theory and comparative analysis methods. Thirty-two parents from 16 families were interviewed in the 1990s, and 22 parents from 10 families in 2020. Ten factors were identified presenting as either enablers or barriers to the family meal, depending on the context they were experienced. Barriers and enablers were largely consistent across time. Scheduling and flexibility, children's disruptions and children's independence, privileges required to have family meals and motivation and commitment to the family meal were identified as persistent enablers and barriers across time. These findings indicate that parents are faced with similar challenges they have been facing for decades and are still not being adequately supported to execute family meals regularly. Recognising that factors present as either barriers or enablers to the family meal provides us with opportunities to transform barriers to enablers and support families to have regular, meaningful family meals.

The family meal, a ritual frozen in time; an Australian grounded theory study.

Family meals are recognized as an opportunity to promote the health of families. Popular discourse posits that changes to contemporary family life have made family meals harder to achieve and promotion of the 'traditional' family meal may be adding pressures to contemporary families. While research has been conducted on family meals over the last three decades, there is no explicit investigation of the experiences and practices of family meals over this time. Understanding the evolution of family meal practices across time is important for developing achievable expectations in relation to this ritual. Qualitative interviews were conducted with a diverse population of South Australian parents in the 1990s (n = 32) and with a separate population of parents in 2020 (n = 22) to gather their experiences of family meal practices. A comparative analysis, informed by grounded theory, was undertaken to identify similarities and differences in experiences across these two time periods. The results indicated stability in many family meal experiences across time, particularly in their value and significance in family life. Negotiations balancing time, cost, food preferences and responsibility persisted. The stability of family meal values and practices is important to consider when making recommendations, designing interventions and creating services targeting the family meal.

Ageing with Interstitial lung disease: preserving health and well being.

PURPOSE OF REVIEW: Ageing, the accrual of molecular and cellular damage over a lifetime confers progressive physiologic dysfunction of bodily systems, leaving the body in a heightened state of vulnerability to biophysical and psychosocial stressors. The inflection point is frailty which easily leads to disability and death. Interstitial lung disease (ILD) creates biophysical and psychosocial stresses difficult for even optimally fit patients to cope with. With evolving ILD treatment pathways, people with ILD are living longer. RECENT FINDINGS: ILD and ageing are bi-directionally influential: ILD, its treatments, complications, and collateral systemic extra-pulmonary damage (hypoxic and oxidative stress) wear on the ageing person and ageing impacts a person's tolerance of ILD. ILD extent may proportionally accelerate age-related vulnerabilities. ILD related to inflammatory systemic diseases, e.g. connective tissue diseases or sarcoidosis, exert an even more complex biophysical impact on the body. SUMMARY: The present review stresses goals of preventing frailty in ILD and preserving general health and well being of people living with ILD of any age, from time of diagnosis and as they age. The development of a prediction score is proposed to classify those at risk of frailty and guide interventions that preserve successful ageing for all levels of ILD severity. VIDEO ABSTRACT: http://links.lww.com/COPM/A32.

Sharing the load: A qualitative exploration of what mothers and fathers believe the father's role should be in food provisioning.

The father's role in household responsibilities has shifted over the past fifty years. In particular, fathers are now expected to be more involved in the family food provisioning but are often still positioned in a role that is supplementary to the mother's role. Previous literature has explored contemporary perceptions of the father's role in this domain, however research on the expectations both parents have for the father's role is limited. This qualitative study therefore seeks to understand what mothers and fathers believe the father's role in family food provisioning should be or what they would like it to be. Semi-structured interviews were used to explore the beliefs, expectations and lived experiences of heterosexual couples (N = 8) with at least one child aged between 5 and 12 years old. A thematic analysis informed by principles of constructivist grounded theory revealed that while the fathers placed importance on equally sharing the food provisioning role, a discrepancy is acknowledged between their attitudes and behaviours. The majority of the mothers desired a more equal share of the food provisioning role. However, such aspirations did not necessarily translate into real-world expectations of the father as they were deemed unlikely to be met. Parents recognised that the birth of children worked to increase the mother's load, and further reinforced the parent's roles moving forward. Constraints to change were heavily impacted by the socialisation of both gender and culture. The current study expands the existing literature by highlighting the need to focus on structural mechanisms that inform cultural and social change, in order to enable a more equal division of food provisioning.

The Family Meal Framework: A grounded theory study conceptualising the work that underpins the family meal.

The family meal has been recognised as an integral part of family life. With the positive health outcomes associated with the family meal, it has been proposed as a strategy for encouraging health-promoting behaviours. However, a detailed understanding of the physical and mental work required to execute the family meal is lacking. The aim of this research was to conduct a grounded theory study to understand the components required to successfully execute the family meal. Two temporal data sets (1993-4/2020) in which diverse participants were sampled were used for this study. Methods used to conduct qualitative interviews with parents in the 1990s were mirrored in the conduct of qualitative interviews with parents in 2020. The interview data was analysed drawing on grounded theory methodology and methods. The entire sample included 54 parents from 28 families. A conceptual framework, 'The Family Meal Framework', was developed from the analyses. The five main components of The Framework are the cognitions (invisible work considering the needs of the family), actions (physical tasks required for the family meal), outcomes (the event of the family meal), the beliefs and feelings (expectations and attitudes toward the family meal), and the person(s) responsible (who undertakes the work). This framework provides a novel theory describing the reactive, cyclical nature of the work required to execute the family meal. This new understanding provides discrete opportunities for intervention in family meal research, practice, policy and promotion.

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that causes early onset pulmonary emphysema and airways obstruction. The complete mechanisms via which AATD causes lung disease are not fully understood. To improve our understanding of the pathogenesis of AATD, we investigated gene expression profiles of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) in AATD individuals. METHODS: We performed RNA-Seq on RNA extracted from matched BAL and PBMC samples isolated from 89 subjects enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Subjects were stratified by genotype and augmentation therapy. Supervised and unsupervised differential gene expression analyses were performed using Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene profiles associated with subjects' clinical variables. The genes in the most significant WGCNA module were used to cluster AATD individuals. Gene validation was performed by NanoString nCounter Gene Expression Assay. RESULT: We observed modest effects of AATD genotype and augmentation therapy on gene expression. When WGCNA was applied to BAL transcriptome, one gene module, ME31 (2312 genes), correlated with the highest number of clinical variables and was functionally enriched with numerous immune T-lymphocyte related pathways. This gene module identified two distinct clusters of AATD individuals with different disease severity and distinct PBMC gene expression patterns. CONCLUSIONS: We successfully identified novel clusters of AATD individuals where severity correlated with increased immune response independent of individuals' genotype and augmentation therapy. These findings may suggest the presence of previously unrecognised disease endotypes in AATD that associate with T-lymphocyte immunity and disease severity.

Granulomatous Inflammation in Tuberculosis and Sarcoidosis: Does the Lymphatic System Contribute to Disease?

A striking and unexplained feature of granulomatous inflammation is its anatomical association with the lymphatic system. Accumulating evidence suggests that lymphatic tracks and granulomas may alter the function of each other. The formation of new lymphatics, or lymphangiogenesis, is an adaptive response to tumor formation, infection, and wound healing. Granulomas also may induce lymphangiogenesis which, through a variety of mechanisms, could contribute to disease outcomes in tuberculosis and sarcoidosis. On the other hand, alterations in lymph node function and lymphatic draining may be primary events which attenuate the risk and severity of granulomatous inflammation. This review begins with an introduction of granulomatous inflammation and the lymphatic system. A role of the lymphatic system in tuberculosis and sarcoidosis is then hypothesized. With a focus on lymphangiogenesis in these diseases, and on the potential for this process to promote dissemination, parallels are established with the well-established role of lymphangiogenesis in tumor biology.

Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

What can families gain from the family meal? A mixed-papers systematic review.

The family meal has been associated with numerous health and wellbeing benefits for both adults and children. However, the majority of the research in this area is correlational, unable to prove a causal relationship between family meals and health and wellbeing outcomes. The objectives of this systematic review were to determine the causal relationship between family meals and health and wellbeing and explore family members' perceptions of the family meal. A systematic search across five databases was undertaken to identify both intervention studies and qualitative studies investigating the family meal. Thirty-two articles were deemed eligible for inclusion in this review. Qualitative data were synthesised via the meta-aggregation approach; however, the quantitative data were too heterogeneous to perform meta-analysis. Only one intervention included in this review exclusively targeted the family meal, the remaining studies had other target strategies as part of their intervention (e.g. physical activity, snacking, sleep routines). Only two of the eight interventions reported a statistically significant difference between control and intervention groups for family meal frequency or quality, therefore we were unable to fully explore the causal relationship between family meals and health and wellbeing outcomes. The qualitative studies identified multiple barriers to the family meal, including scheduling conflicts, exhaustion and lack of time, and reported family connection and communication as the main perceived benefits of the family meal. There is a gap between the benefits and barriers to the family meal identified through qualitative research, and current intervention strategies, with few interventions exclusively targeting the family meal. Interventions that are informed by qualitative literature and exclusively target the family meal are needed to further investigate the causal relationship between family meals and potential health and wellbeing outcomes.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

Microbial Lineages in Sarcoidosis. A Metagenomic Analysis Tailored for Low-Microbial Content Samples.

RATIONALE: The etiology of sarcoidosis is unknown, but microbial agents are suspected as triggers. OBJECTIVES: We sought to identify bacterial, fungal, or viral lineages in specimens from patients with sarcoidosis enriched relative to control subjects using metagenomic DNA sequencing. Because DNA from environmental contamination contributes disproportionately to samples with low authentic microbial content, we developed improved methods for filtering environmental contamination. METHODS: We analyzed specimens from subjects with sarcoidosis (n = 93), control subjects without sarcoidosis (n = 72), and various environmental controls (n = 150). Sarcoidosis specimens consisted of two independent sets of formalin-fixed, paraffin-embedded lymph node biopsies, BAL, Kveim reagent, and fresh granulomatous spleen from a patient with sarcoidosis. All specimens were analyzed by bacterial 16S and fungal internal transcribed spacer ribosomal RNA gene sequencing. In addition, BAL was analyzed by shotgun sequencing of fractions enriched for viral particles, and Kveim and spleen were subjected to whole-genome shotgun sequencing. MEASUREMENTS AND MAIN RESULTS: In one tissue set, fungi in the Cladosporiaceae family were enriched in sarcoidosis compared with nonsarcoidosis tissues; in the other tissue set, we detected enrichment of several bacterial lineages in sarcoidosis but not Cladosporiaceae. BAL showed limited enrichment of Aspergillus fungi. Several microbial lineages were detected in Kveim and spleen, including Cladosporium. No microbial lineage was enriched in more than one sample type after correction for multiple comparisons. CONCLUSIONS: Metagenomic sequencing revealed enrichment of microbes in single types of sarcoidosis samples but limited concordance across sample types. Statistical analysis accounting for environmental contamination was essential to avoiding false positives.

Brief Participant-Centered Convergence Interviews Integrate Self-Reports, Product Returns, and Pharmacokinetic Results to Improve Adherence Measurement in MTN-017.

MTN-017 compared the safety and acceptability of daily oral emtricitabine/tenofovir disoproxil fumarate, daily reduced-glycerin 1% tenofovir gel applied rectally, and the same gel applied before and after receptive anal intercourse. The Data Convergence Interview (DCI) and the Pharmacokinetic Data Convergence Interview (PK-DCI) were brief, collaborative interactions conducted with participants during adherence counseling sessions to improve accurate measurement of adherence to study product use. DCIs converged data from product return counts and participants' responses to daily text messages. PK-DCIs, conducted 4 weeks later, converged results of the DCI with PK from the corresponding period. CIs were easily incorporated into adherence counseling sessions, increased the accuracy of adherence data, and provided valuable context to data on product use. Participants were readily engaged in the interviews but, if they felt confronted, provided more guarded responses. As such, how these CIs are conducted is critical to engage participants, even those with poor adherence, to openly discuss challenges with product use.

The role of nailfold capillary dropout on mortality in systemic sclerosis.

BACKGROUND: Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. AIM: To investigate the possible utility of NFC in predicting survival. METHODS: Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. RESULTS: The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log-rank χ2 = 8.75, P = 0.003) and antibody status (log-rank χ2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P < 0.001). In Cox regression, adjustment for capillary dropout attenuated the impact of autoantibody group on survival. CONCLUSIONS: Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality.

MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel.

Background: Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. Methods: MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. Results: MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in ≥grade 2 adverse event rates between daily gel (incidence rate ratio [IRR], 1.09; P = .59) or RAI gel (IRR, 0.90; P = .51) compared to FTC/TDF. High adherence (≥80% of prescribed doses assessed by unused product return and Short Message System reports) was less likely in the daily gel regimen (odds ratio [OR], 0.35; P < .001), and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR, 0.38; P < .001). Conclusions: Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen. Clinical Trials Registration: NCT01687218.

From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis.

PURPOSE OF REVIEW: Up to twenty percent of patients with sarcoidosis develop pulmonary fibrosis, transforming an often benign disease into a highly morbid and potentially fatal one. We highlight the fibrotic pulmonary sarcoidosis phenotype as an area of intense clinical and translational investigation, review recent developments in treatment, and provide a roadmap for future research in sarcoidosis associated pulmonary fibrosis. RECENT FINDINGS: Granulomatous inflammation in a lymphatic distribution is the hallmark finding of pulmonary sarcoidosis and the nidus for fibrosis. Recent research demonstrates that fibrotic sarcoidosis begins in the setting of persistent, uncontrolled inflammation, and is aided by pro-fibrotic genetic features and immune responses. Comparison to other fibrotic lung diseases also reveals key features that inform our understanding of common pathways in fibrosis. SUMMARY: Understanding the mechanisms of fibrotic transformation in sarcoidosis enhances clinical care and facilitates development of novel therapeutic options. The impact of these findings in fibrotic sarcoidosis may be amplified through application to other interstitial lung diseases marked by inflammatory to fibrotic transformation. Important aspects of clinical management of fibrotic sarcoidosis include surveillance for co-morbidities, such as pulmonary hypertension, airway disease, and infection, and assessment for pulmonary disease activity that may benefit from immunosuppression.