Chronic histiocytic intervillositis: A breakdown in immune tolerance comparable to allograft rejection?

Brady, Chloe A.; Williams, Charlotte L.; Sharps, Megan; Shelleh, Amena; Batra, Gauri; Heazell, Alexander E P; Crocker, Ian

doi:10.1111/aji.13373

Cited by 22 publications

(31 citation statements)

References 118 publications

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“…21 Clinical aspect CHI has been associated with poor perinatal outcomes, including intrauterine fetal demise (IUFD) and FGR, and typically shows recurrence in subsequent pregnancies. [16][17][18][19][20][21][22] Our experience with CHI showed an IUFD of 22%, FGR of 50%, and recurrences of 17%. 21…”

Section: Histological Findingsmentioning

confidence: 70%

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Inflammatory lesions in placental pathology

Sato

2021

J of Obstet and Gynaecol

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Placental inflammatory lesions are important findings that lead fetal and neonatal morbidity and mortality, and can be divided into two broad subcategories, acute inflammation caused by microorganisms and chronic inflammation caused by host immune responses. Recently, a diagnostic framework for these lesions has been established, and uniform diagnostic criteria have been recommended by the Amsterdam International Consensus Group. Chorioamnionitis is representative of the acute inflammatory lesion, and is the most frequent pathological diagnosis in placental pathology. The hallmark of chorioamnionitis is neutrophil infiltration in the membrane/chorioamnionic plate and fetal vessels. The inflammatory response can be both maternal (inflammation in the membrane or chorioamnionic plate) and fetal (inflammation in the fetal vessels-umbilical vessels or chorionic vessel). Recent studies have shown that the fetal inflammatory response is associated with neonatal mortality and morbidity. Furthermore, chronic inflammatory lesions, such as villitis of unknown etiology and chronic histiocytic intervillositis, are also important. Although their etiology remains unknown, the maternal immune response against paternal antigens has been considered a possible factor. These inflammatory lesions are associated with fetal demise and fetal growth restriction. Inflammatory lesions in the placenta are useful for understanding intrauterine conditions, guiding treatment, and predicting complications.

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Section: Histological Findingsmentioning

confidence: 70%

“…18 The etiology remains unknown, and several studies suggest that CHI represents an adaptive immune response to antigens, possibly paternally derived, on the trophoblastic surface. 19…”

Section: Clinical Aspectmentioning

confidence: 99%

Inflammatory lesions in placental pathology

Sato

2021

J of Obstet and Gynaecol

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“…In the absence of an infectious cause, attention should focus on an immune-mediated pathophysiology. Parallels with transplant immunology have led some groups to describe VUE, CHI and MPFD as analogous to maternal "rejection" of the fetal semi-allograft (13,72,83,108,109). However, unlike solid organ allografts, serial sampling of the placenta during pregnancy is impossible given the associated risks to both mother and fetus.…”

Section: Chronic Placental Inflammation and Infectionmentioning

confidence: 99%

“…VUE affects 5-15% of placentas (9), CHI 0.2% (10), and MPFD 0.5% (11). The underlying disease mechanisms are poorly understood and there are no biomarkers or treatment protocols that can reliably predict or prevent recurrence in a subsequent pregnancy (12,13).…”

Section: Introductionmentioning

confidence: 99%

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

2022

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Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.

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“…Chronic histiocytic intervillositis (CHI) (also referred as CHIV) is a rare but severe placental condition characterised by the presence of an inflammatory mononuclear infiltrate in the intervillous space. CHI has been estimated to affect 6 in every 10 000 pregnancies that reach 12 weeks gestation (1,2) and the term was first introduced by Labarrere and Mullen in 1987 as massive chronic intervillositis (3). This pathology has since been referred to by several names across the literature, including chronic intervillositis of unknown aetiology (CIUE), massive chronic intervillositis, massive perivillous histiocytosis and shortened forms -chronic intervillositis or intervillitis.…”

Section: Introductionmentioning

confidence: 99%

Chronic histiocytic intervillositis (CHI): current treatments and perinatal outcomes, a systematic review and a meta-analysis

et al. 2022

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BackgroundChronic histiocytic intervillositis (CHI) is a rare placental lesion with a high recurrence rate and poor perinatal outcomes. There are currently limited guidelines regarding the diagnosis of this condition in the index pregnancy and treatment where recurrence is suspected.ObjectiveThe primary objective of this systematic review and meta-analysis was to determine the perinatal outcomes of pregnancies affected by chronic histiocytic intervillositis and to what extent they can be improved with treatment. The secondary objective was to assess the relationship between CHI lesion severity and pregnancy loss.MethodsA systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. Case reports, cohort, case-control and randomised controlled trials (RCT) detailing the perinatal outcomes of CHI pregnancies, both treated and untreated, were included.ResultsNo RCTs were identified. However, in a review population of 659 pregnancies, with additional 7 in case reports, CHI treatments included aspirin, prednisone, prednisolone, low molecular weight heparin (LMWH), hydroxychloroquine and adalimumab. A descriptive synthesis of data found mixed results for treatments in relation to live birth, miscarriage and fetal growth restriction outcomes. Furthermore, quantitative synthesis of 38 pregnancies revealed a non-significant improvement in live birth rate with CHI targeted treatment (OR 1.79 [95% CI 0.33-9.61] (p=0.50), while meta-analysis of CHI severity in line with pregnancy loss, in a sample of 231 pregnancies, revealed lower odds of pregnancy loss with less severe lesions (OR: 0.17 [0.03-0.80], p=0.03).ConclusionsThis systematic review and meta-analysis reinforce notions surrounding the insufficient evidence for CHI treatment. It also strengthens previous hypotheses detailing the positive association between CHI lesion severity and odds of pregnancy loss. Aspirin, LMWH, prednisolone, hydroxychloroquine and adalimumab are candidates with varying levels of weak to moderate evidence supporting their use. Further prospective research is required to obtain robust evidence pertaining to treatment safety and efficacy and optimal drug regimes.Systematic Review Registration[website], identifier CRD42021237604

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Chronic histiocytic intervillositis: A breakdown in immune tolerance comparable to allograft rejection?

Cited by 22 publications

References 118 publications

Inflammatory lesions in placental pathology

Inflammatory lesions in placental pathology

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

Chronic histiocytic intervillositis (CHI): current treatments and perinatal outcomes, a systematic review and a meta-analysis

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