Late HIV presentation to care:Earlier HIV diagnosis in Primary Health Care & Long-term survival & Tuberculosis co-infection

Trods en opmuntrende nedadgående tendens i den globale hiv-incidens, er sen hiv-diagnose fortsat et problem i håndteringen af hiv, hvor stadig halvdelen af nye hiv-patienter diagnosticeres i sene stadier af sygdommen. Til trods for en omfattende folkesundhedsindsats har omfanget af sen HIV-diagnose ligget stort set uændret igennem det sidste årti. Sen hiv-diagnose medfører øget sygelighed og dødelighed, lavere livskvalitet, dårligere immunrestitution, vedvarende kronisk inflammation, højere sundhedsudgifter og øget risiko for videre spredning af infektionen i samfundet. Personer, der ikke tilhører de traditionelle HIVrisikogrupper, såsom heteroseksuelle mænd, kvinder og ældre patienter, såvel som ikke-europæiske individer, har en højere risiko for sen hiv-diagnose. Den første gruppe kan primært tilskrives lægers (og patienters) lave kliniske mistanke om udiagnosticeret hiv-infektion, mens sidstnævnte forekommer kontraintuitiv, da mange individer fra ikke-europæiske lande kommer fra hiv-endemiske områder.Der findes forskellige retningslinjer for hiv-testning. De europæiske retningslinjer anbefaler rutinemæssig hiv-screening hos alle gravide kvinder og målrettet hiv-testning i højrisikogrupper for hiv og i tilfælde af hivindikator sygdomme. På trods af disse anbefalinger tilbydes mange patienter ikke en hiv-test i de to sidstnævnte situationer, såkaldte ”missed oppurtunities” for tidligere hiv-diagnose. Disse ”missed oppurtunities” er hyppige, og i nogle undersøgelser er der rapporteret så høje tal som 70-80 % af alle nydiagnosticerede PLWH, der har haft mindst én ”missed oppurtunity” for tidligere hiv-diagnose. Almen praksis fungerer som frontlinje kontakt til sundhedsvæsnet og har en afgørende rolle for at diagnosticere disse patienter tidligt med proaktiv hiv-test.I undersøgelserne inkluderet i denne afhandling kiggede vi på adfærdsmæssige aspekter og risikofaktorer, relateret til almen praksis, forbundet med hiv-infektion, med henblik på at kunne forbedre effektiviteten af hiv-test strategier. For de PLWH, der allerede blev diagnosticeret på et sent stadium af infektionen, undersøgte vi prognostiske faktorer for langsigtet overlevelse og ukomplet immunrestitution. Endelig undersøgte vi TB-risiko og tilhørende dødelighed i PLWH, da TB stadig er en af de mest almindelige AIDSdefinerende opportunistiske infektioner på verdensplan hos patienter med sene hiv diagnose.Studie I og II blev designet som nested matchede case-control undersøgelser. Fra den danske hiv-kohorte inkluderede vi alle voksne PLWH diagnosticeret med hiv mellem 1998-2015 og bosat i Danmark i ≥3 år ved hiv-diagnosen. Fra det Danske CPR-register inkluderede vi alders- og kønsmatchede kontroller (13:1). I alt 2784 hiv-smittede individer og 36.192 matchede kontroller blev inkluderet i analysen. Vi fandt, at PLWH hyppigt besøgt deres praktiserende læger i de tre år der gik forud for hiv-diagnosen. Faktisk havde 93% af PLWH besøgte almen praksis mindst én gang i denne periode, med et mediantal af besøg på 14. Desuden observerede vi, at PLWH havde et højere forbrug af antimikrobielle midler sammenlignet med kontroller i de 3 år før hiv-diagnose. Vi fandt en statistisk signifikant association mellem forbrug af alle antimikrobielle lægemidler inkluderet i studiet og risiko for senere hiv diagnose. Associationen var mere udtalt jo højere niveauet af antimikrobielt forbrug var. Selvom vi ikke havde adgang til information om indikation til recepterne, antager vi, at brugen af antimikrobielle lægemidler i mange tilfælde var en surrogatmarkør for hiv-indikator sygdomme (f.eks. samfundserhvervet lungebetændelse, STI'er, herpes zoster eller candidiasis).Studie III var designet som et kohortestudie. Fra den catalanske hiv PISCIS-kohorte inkluderede vi alle voksne PLWH, der initierede ART mellem 2005-2019, som var i live 2 år efter, med tilgængeligt CD4-celletal ved ART-opstart og to år efter (n=2719). Vi fandt at, på trods af den sene hiv-diagnose, opnåede 44% af dem der overlevede de første 2 år efter ART start et CD4-celletal &gt;500 celler/µL. To-års CD4-tallet var en stærk uafhængig tidlig markør for langsigtet dødelighed, uafhængigt af CD4-celletallet ved ART-start. Hivsmittede med sen diagnose og med to-års CD4-tal &gt;500 celler/µL havde samme overlevelse som ikke-sendiagnosticeret. Endvidere var opstart af ART med et integrase-hæmmer (INSTI)-baseret regime i de første to år forbundet med en signifikant bedre to-års immunrestitution og bedre langtidsoverlevelse.Studie IV var designet som et nationalt populations-baseret kohortestudie. Vi inkluderede 6982 PLWH fulgt for hiv i Danmark mellem 1995-2017. To hundrede og sytten patienter udviklede TB i studieperioden. Studiet identificerede to forskellige populationer af hiv/TB co-inficerede individer: individer med samtidig hiv/TB-infektion (hyppigere migranter, LP med en højere procentdel af dissemineret TB) og individer, der blev diagnosticeret med TB &gt;3 måneder fra hiv-diagnosen (median tid fra hiv-diagnosen til TB 5,1 år, hyppigere danskfødte, med en højere social belastning, højere forekomst af lever- og ikke-TB AIDSrelaterede sygdomme, en højere procentdel af lunge-TB og med en højere risiko for suboptimal kobling til pleje). Sidstnævnte gruppe havde et værre TB-outcome med hyppigere behandlingsophør og død. Forekomsten af samtidig hiv/TB co-infektion forblev høj og uændret over undersøgelsesperioden, mens forekomsten af TB diagnosticeret &gt;3 måneder efter hiv-diagnose faldt over tid, sandsynligvis relateret til bedre ART, ART-dækning og tidligere ART-initiering. Risikoen for TB faldt også med tiden fra hiv-diagnosen og med stigning i CD4-tal. Ingen individ modtog behandling for latent TB-infektion (LTBI). Migration, iv misbrug, ikke at være i ART og hiv-relateret immunsuppression blev identificeret som risikofaktorer for at udvikle TB. Dødelighed af co-inficerede individer forblev høj over tid, og hiv-associeret immunsuppression, dissemineret TB og social belastning blev fundet at være signifikante prognostiske faktorer for død hos disse patienter.Mulighed for at minimere forekomsten af sen hiv-diagnose er et kritisk vendepunkt for yderligere at bremse hiv-epidemien globalt og forbedre hiv-prognosen. Almen praksis kan spille en vigtig rolle i rettidig hiv diagnose, da &gt;90% af hiv patienter besøger almen praksis i årene før deres diagnose. Der er således behov for mere proaktiv testning i almen praksis, bedre implementering af eksisterende retningslinjer for hiv-testning samt andre og nye strategier. Opmærksomhed omkring et individs forbrug af antimikrobielle midler kunne være én mulighed og anvendes som et værktøj til vejledning for, hvornår en hiv-test bør udføres i almen praksis. Et sådant værktøj kunne lette integrationen i den daglige klinik og medvirke til normaliseringen af hiv-test i almen praksis og hermed undgå nogle af de kendte barrierer for hiv-test samt hjælpe til at mindske hiv-relateret stigma.Hos LP er to-års CD4-tal en god tidlig markør af langtidsoverlevelse, meget mere præcis end det initiale CD4-tal, og denne parameter vil kunne bruges i klinikken til at orientere patientens prognose. Desuden peger vores resultater på at INSTI-baseret ART kan overvejes som første valg regimer. INSTI var forbundet med en signifikant bedre to-års immunrestitution og langtidsoverlevelse i LP. Endelig fandt vi, at TB-raten i PLWH faldt over tid og sideløbende med stigning i CD4-tal, hvilket understreger vigtigheden af tidlig HIV-diagnose og vellykket ART. På grund af den høje forekomst af sen hivdiagnose med samtidig TB, er en mere proaktiv hiv-testning og TB-forebyggende foranstaltninger påkrævet. Migration, IDU og hiv-induceret immunsuppression er alle blevet identificeret som vigtige risikofaktorer for TB og understreger vigtigheden af rutinemæssig screening og behandling af LTBI i disse højrisikogrupper i lande med lav TB-forekomst.Delay in HIV diagnosis carries important consequences for both the individual and society. While there is an encouraging decreasing trend in the global HIV incidence, late HIV diagnosis remains a blot in the management of HIV, with still half of new HIV patients presenting at late stages of the disease at the time of diagnosis. Despite public health efforts, the magnitude of late HIV diagnosis has remained unchanged over the last decade. Late HIV diagnosis leads to increased morbidity and mortality, lower life quality, poorer immune reconstitution, persistent chronic inflammation, higher health care costs, and increased risk of onward transmission in the population before diagnosis. Individuals not belonging to the traditional HIV risk groups, such as heterosexual men, females, and older patients, as well as non-European individuals, are at a higher risk of late HIV diagnosis. The first group is primarily attributable to physicians’ (and patients’) low clinical suspicion of undiagnosed HIV, but the latter is counterintuitive given that many individuals from non-European countries come from HIV-endemic areas.Various guidelines have been developed to better target patients for HIV testing. The European guidelines recommend routine HIV screening in pregnant women and targeted HIV testing in high-risk groups for HIV acquisition and in case of presenting to care with an HIV indicator condition. Despite these recommendations, many patients are not offered an HIV test in the latter two situations, so-called missed opportunities for earlier HIV diagnosis. These missed opportunities are frequent, and some studies have reported figures as high as 70-80% of newly diagnosed PLWH having had at least one missed opportunity for earlier HIV diagnosis. Primary health care (PHC) serves as the frontline service and is pivotal in facilitating early HIV diagnosis through provider-initiated HIV testing. Thus, engaging PHC could improve timely HIV diagnosis and, ultimately, HIV prognosis.In the studies included in this thesis, we investigated behavioural aspects and risk factors related to PHC associated with HIV infection to improve the effectiveness of HIV testing strategies. For those PLWH where “the damage had already occurred” and were unfortunately diagnosed at a late stage of the infection, we evaluated determinants for long-term survival and incomplete immune recovery. Finally, we assessed TB risk and associated mortality in PLWH as TB is still one of the most common AIDS-defining opportunistic infections worldwide in late HIV presenters.Studies I and II were designed as matched case-control studies. From the Danish HIV Cohort, we included all adult PLWH diagnosed with HIV between 1998-2015 and living in Denmark for ≥3 years at HIV diagnosis. From the population, we included age- and gender-matched controls (13:1). In total 2784 HIV cases and 36,192 population controls were included in the analysis. We found that PLWH frequently attended PHC in the three years preceding HIV diagnosis. Actually, 93% of PLWH had attended PHC at least once in this period, with a median number of visits of 14. Only 4% and 13% of Danish-born and non-Danish-born men and 3% and 26% of Danish-born and non-Danish-born women had had no contact with PHC in the previous three years of HIV diagnosis. Besides, we observed that PLWH had a higher prescription of antimicrobials compared to controls in the 3 years before HIV diagnosis. The antimicrobial drug prescription of any of the antimicrobial drug classes included in the study was associated with the risk of subsequent HIV diagnosis. This association was higher with higher levels of antimicrobial consumption. Although we did not dispose of indication information for the prescriptions, we assume that the use of antimicrobial drugs was in many cases a surrogate marker for missed HIV indicator conditions (e.g., community-acquired pneumonia, STIs, herpes zoster, or candidiasis). Study III was designed as a cohort study. From the Catalan HIV PISCIS cohort, we included all adult PLWH initiating ART between 2005-2019, who were alive 2 years after, with available CD4 cell count at ART initiation and two years after (n=2719). We found that despite the late HIV diagnosis, 44% of 2-year 11 survivors’ late presenters achieved a CD4 cell count &gt; 500cells/µL after ART initiation. Two-year CD4 count recovery was a strong independent early predictor for long-term all-cause mortality, independently of the CD4 cell count at ART initiation. Importantly, late HIV presenters with two-year CD4 count &gt;500 cells/µL had similar survival to non-late presenters. Furthermore, initiating ART with an integrase-inhibitor (INSTI)- based regimen in the first two years was associated with a significantly better two-year immune recovery and better long-term survival.Study IV was designed as a nationwide population-based cohort study. We included 6982 PLWH followedfor-HIV-care in Denmark between 1995-2017. Overall, 217 develop TB in the study period. Two different populations of HIV/TB coinfected individuals were identified: those presenting to care with concomitant HIV/TB infection (more frequently migrants, late presenters with a higher percentage of disseminated TB) and those diagnosed with TB &gt;3 months from HIV diagnosis (median time from HIV diagnosis to TB 5.1 years (IQR 2.0-9.6), more frequently Danish-born individuals, with a higher social burden, higher rates of liver and non-TB AIDS-related comorbidities, a higher percentage of pulmonary TB and with a higher risk of suboptimal linkage to care). The latter had a worse TB outcome, with higher rates of treatment discontinuation and death. The incidence of concomitant HIV/TB coinfection remained high and unchanged over the study period, while the incidence of TB diagnosed &gt;3 months after HIV diagnosis, declined over time, probably related to better ART, ART coverage, and earlier ART initiation. The risk of TB also declined with time from HIV diagnosis and with CD4 immune recovery. No individual had received treatment for latent TB infection (LTBI). Migration, history of IDU, not receiving ART, and HIV-induced immune suppression were identified as risk factors for developing TB. The overall mortality rate in PLWH co-infected with TB remained high over time and HIV-associated immunosuppression, disseminated TB, and social burden were found to be significant predictors of death in these patients.Taken together, the loss of diagnostic opportunities for HIV diagnosis represents a critical turning point to further curb the HIV epidemic globally and improve HIV prognosis. PHC is frequently attended by individuals with undiagnosed HIV infection and should provide numerous opportunities for HIV testing. There is thus a need for more proactive testing in PHC, implementing existing HIV testing guidelines and other novel strategies. Some particular antimicrobial consumption is associated with a higher subsequent risk of HIV diagnosis and could be used as a marker to prompt proactive testing of HIV infection. Using electronic health record alerts, this strategy could be easily implemented in PHC helping reduce counselling time and contributing to the normalization of HIV testing and the reduction of HIV-related stigma. In LP, two-year CD4 cell recovery is a good early predictor of long-term survival, much more precise than initial baseline CD4 cell counts, and this parameter could be used in routine clinical practice to early orient the patient’s clinical trajectory. Furthermore, our findings support the positioning of INSTI-based ART as preferred regimens. INSTI were associated with a significantly better two-year immune recovery and, importantly, better outcomes including long-term survival in LP, though additional research is required to confirm our findings.Finally, we found that TB rates in PLWH decreased over time and paralleled CD4 cell recovery, which emphasizes the importance of early HIV diagnosis and successful ART. Due to the continually high incidence of late HIV presentation with concomitant TB, more proactive HIV testing, and TB prevention measures are required. Migration, IDU, and HIV-induced immunosuppression have all been identified as important risk factors for TB and underline the importance of routine screening and treatment of LTBI in these high-risk groups in low-TB incidence countries.<br/

Incidence of Sexually Transmitted Infections After Initiating HIV Pre-Exposure Prophylaxis Among MSM in Southern Denmark

Pre-exposure prophylaxis (PrEP) is a new preventive treatment for individuals at high-risk for HIV infection, such as men who has sex with men (MSM). Studies have confirmed the efficacy but concerns about the potential induction of risk compensation remains. We aimed to assess the incidence of sexually transmitted infections (STIs) after PrEP initiation as a proxy for sexual risk behavior. This case-crossover study used data from medical records and from the Danish Microbiology Database from patients who initiated PrEP at the Region of Southern Denmark between 2017 and 2019. Poisson regression was used to assess STI incidence 6 months after PrEP initiation versus the 6 months before. To identify potential risk factors, we compared individuals with an increased STI incidence after PrEP initiation with those without, using logistic regression. In total, 46 MSM initiated PrEP in the study period. We found a significant increase in the number of positive samples for STI after PrEP initiation (IRR 1.83; 95% CI [1.03, 3.26]) and a tendency for higher incidence of STI episodes (1.67; 95% CI [0.91, 3.13]). The increase was concentrated to a group of users, but no significant correlation was found between increasing incidence and the baseline factors examined. We observed a degree of risk compensation after the implementation of PrEP among MSM, clustering to a group of users. Our results highlight the importance of frequent STI screening among MSM on PrEP as timely diagnosis could contribute to an overall decrease in STI incidence and incidence among MSM.</p

Strongyloides stercoralis hyperinfection syndrome with cerebral involvement.

Strongyloidiasis is a disease caused by the intestinal helminth Strongyloides stercoralis When the immune system of infected individuals is compromised, larvae may migrate from the gastrointestinal tract to other tissues, causing S. stercoralis hyperinfection syndrome, which has a reported mortality of 71%. In this case, we report a patient with S. stercoralis hyperinfection syndrome with central nervous system (CNS) involvement. An elderly South East Asian male tourist presented with pulmonary symptoms, fever and infiltrates on chest X-ray. He later developed symptoms of CNS infection. S. stercoralis larvae were found in a stool sample. Microbiological examination of cerebrospinal fluid revealed S. stercoralis-specific DNA. The patient was treated with oral and rectal ivermectin and albendazole. The condition was complicated by sepsis, bacteraemia and hypereosinophilia. Unfortunately, the patient eventually died from pulmonary oedema and insufficiency. This case highlights the global importance of Strongyloides CNS infection in endemic and non-endemic regions. </p

Arcobacter butzleri is an opportunistic pathogen:recurrent bacteraemia in an immunocompromised patient without diarrhoea

Introduction: Arcobacter butzleri is attracting increasing interest due to its possible pathogenic properties. Researchers have described cases in which A. butzleri is isolated in stool samples from patients with gastrointestinal symptoms, mostly diarrhoea. The relevance of adding our case to the literature lies in its description of recurrent A. butzleri bacteraemia in a patient without diarrhoea.Case presentation: An immunocompromised patient was hospitalized three times within 12 months due to A. butzleri-induced bacteraemia. At no time did the patient experience diarrhoea even though examination of stool samples showed growth of A. butzleri . The isolate was susceptible to gentamicin, colistin and tetracyclines. The patient was successfully treated with doxycycline.Conclusion: For the first time in the literature we describe recurrent A. butzleri bacteraemia in a patient without diarrhoea. This case supports the classification of A. butzleri as an opportunistic pathogenic species, which clinical microbiology laboratories should be able to identify.</p

Prescription of antimicrobials in primary health care as a marker to identify people living with undiagnosed HIV infection, Denmark, 1998 to 2016

BackgroundDevelopment of additional diagnostic strategies for earlier HIV diagnosis are needed as approximately 50% of newly diagnosed HIV-infected individuals continue to present late for HIV care.AimWe aimed to analyse antimicrobial consumption in the 3 years preceding HIV diagnosis, assess whether there was a higher consumption in those diagnosed with HIV compared with matched controls and whether the level of consumption was associated with the risk of HIV infection.MethodsWe conducted a nested case-control study, identifying all individuals (n = 2,784 cases) diagnosed with HIV in Denmark from 1998 to 2016 and 13 age-and sex-matched population controls per case (n = 36,192 controls) from national registers. Antimicrobial drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals.ResultsIn the 3 years preceding an HIV diagnosis, we observed more frequent and higher consumption of antimicrobial drugs in cases compared with controls, with 72.4% vs 46.3% having had at least one prescription (p &lt; 0.001). For all antimicrobial classes, the association between consumption and risk of subsequent HIV diagnosis was statistically significant (p &lt; 0.01). The association was stronger with higher consumption and with shorter time to HIV diagnosis.ConclusionHIV-infected individuals have a significantly higher use of antimicrobial drugs in the 3 years preceding HIV diagnosis than controls. Prescription of antimicrobial drugs in primary healthcare could be an opportunity to consider proactive HIV testing. Further studies need to identify optimal prescription cut-offs that could endorse its inclusion in public health policies.</p

Pneumocystis Pneumonia—Is it Still a Threat Among People With Human Immunodeficiency Virus (HIV)?:A Danish HIV Cohort Study

Background We aimed to examine pneumocystis pneumonia (PCP) risk and mortality among people with human immunodeficiency virus (HIV), and associations with (1) time after HIV diagnosis, (2) calendar time, and (3) CD4 cell count. Methods From the Danish HIV cohort study, we identified all adult people with HIV (PWH) (1995-2021). We estimated incidence rates (IRs) and mortality rates. We used Poisson regression analysis to compute adjusted incidence ratios (IRRs) and mortality rate ratios. PCP risk was assessed according to time after HIV diagnosis, calendar time, and low CD4 cell count. Results Among 4882 PWH (53 647 person-years), we observed 336 PCP events (for the time period 2016-2021 compared to 1995-1999, PCP risk decreased by &gt;90% after the first year of HIV diagnosis; aIRR, 0.08 [95% confidence interval {CI},. 02-.29], and by &gt;40% in the first year, if baseline CD4 count was &lt;200 cells/μL [aIRR, 0.57 [95% CI,. 36-.90]). However, no statistically significant change in PCP risk was observed after 1995-1999 for the latter group. PCP risk remained high if the CD4 count was 100 to &lt;200 cells/μL (IR, 16.08 [95% CI, 5.19-49.89]) during the first year of combination antiretroviral therapy (cART), despite a suppressed viral load. Major reductions were found after 1 year of cART (CD4 count 100 to &lt;200 cells/μL). Although nonsignificant, the 3- and 12-month mortality rate decreased by 80% from 1995-1999 to 2016-2021. Conclusions PCP remains a significant problem among late presenters with HIV, emphasizing the importance of early HIV diagnosis. Continuing PCP prophylaxis until the CD4 count is &gt;100 cells/μL, with at least 1 year of cART and viral suppression for &gt;3 months should be considered; however; further studies are needed to confirm these results.</p

Emergent Human Immunodeficiency Virus Type 1 (HIV-1) Drug Resistance in Randomized Trials of Contemporary Antiretroviral Regimens

The occurrence of virological failure in a subset of individuals is an inevitable aspect of antiretroviral treatment, and historically has been primarily influenced by suboptimal adherence to oral therapies. The risk of selecting 1- or 2-class human immunodeficiency virus (HIV) drug resistance is influenced by the composition of the regimen, differing significantly depending on the intrinsic barrier to resistance of the regimen. HIV resistance emergence during treatment can be viewed as a regimen-related adverse effect that warrants equal consideration in clinical trials alongside virological and safety endpoints. Antiretroviral regimens demonstrating non-inferiority and showing similar rates of virological failure can nonetheless differ in terms of HIV emergent resistance. We propose the development of a systematic framework to categorize emergent HIV drug resistance in clinical trials. Standardizing the evaluation of resistance in clinical trials and its reporting to regulatory agencies will facilitate an improved understanding of regimen-specific resistance risks and better inform clinical decision making.The intrinsic barrier to resistance of an antiretroviral regimen modulates the emergent HIV resistance during virological failure episodes. HIV resistance emergence during treatment warrants consideration in randomized clinical trials equivalent to virological and safety endpoints and should be standardized

A retrospective cohort study of patients with eosinophilia referred to a tertiary centre

Introduction. Patients with eosinophilia (an increased number of eosinophilic granulocytes &gt; 0.5 × 109/l in the blood) are encountered in all medical specialties and frequently need thorough workup to identify the eliciting causes and decide whether treatment is indicated. In Denmark, highly specialised centres for eosinophilic diseases or conditions have been established to provide a foundation for the management of complicated cases. Here, we present experiences from such a multidisciplinary centre. Methods. This was a retrospective study of all patients seen in our tertiary centre for eosinophilia in the 2016-2019 period. Results. Referrals mainly derived from specialised secondary care and to a lesser degree from primary care physicians. Patients were either asymptomatic or exhibited symptoms from up to three organ systems and presented a median eosinophil count of 1.7 × 109/l. Up to eight new clonality analyses or imaging studies per patient were performed after referral. One of these, T-cell receptor analysis, was performed frequently but provided limited information, whereas, e.g., flow cytometry proved more clinically applicable owing to its broader diagnostic range. In total, 51 patients were evaluated and classified as secondary (59%), myeloid neoplasm with PDGFRA rearrangement (2%), idiopathic hypereosinophilic syndrome (31%) and idiopathic hypereosinophilia (8%). Conclusion. The value of a multidisciplinary and versatile approach in a highly specialised centre has a positive impact on diagnostic processes as well as on the evaluation of treatment need.</p

A retrospective cohort study of patients with eosinophilia referred to a tertiary centre

Introduction. Patients with eosinophilia (an increased number of eosinophilic granulocytes &gt; 0.5 × 109/l in the blood) are encountered in all medical specialties and frequently need thorough workup to identify the eliciting causes and decide whether treatment is indicated. In Denmark, highly specialised centres for eosinophilic diseases or conditions have been established to provide a foundation for the management of complicated cases. Here, we present experiences from such a multidisciplinary centre. Methods. This was a retrospective study of all patients seen in our tertiary centre for eosinophilia in the 2016-2019 period. Results. Referrals mainly derived from specialised secondary care and to a lesser degree from primary care physicians. Patients were either asymptomatic or exhibited symptoms from up to three organ systems and presented a median eosinophil count of 1.7 × 109/l. Up to eight new clonality analyses or imaging studies per patient were performed after referral. One of these, T-cell receptor analysis, was performed frequently but provided limited information, whereas, e.g., flow cytometry proved more clinically applicable owing to its broader diagnostic range. In total, 51 patients were evaluated and classified as secondary (59%), myeloid neoplasm with PDGFRA rearrangement (2%), idiopathic hypereosinophilic syndrome (31%) and idiopathic hypereosinophilia (8%). Conclusion. The value of a multidisciplinary and versatile approach in a highly specialised centre has a positive impact on diagnostic processes as well as on the evaluation of treatment need.</p