How is the periconceptional period managed in patients with vasculitis? The first comprehensive guide publishes the guideline consensus

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Vasculitis is a general term for a class of diseases that cause inflammation of blood vessels, clinically manifested as damage to single or multiple organ systems, and some types of vasculitis can affect the reproductive health
of patients.
The American College of Rheumatology (ACR), the American College of Obstetricians and Gynecologists (ACOG), the European Board of Obstetricians and Gynecologists (EBCOG), and the European Union Against Rheumatism (EULAR) have developed reproductive health management guidelines for rheumatology patients, but have not proposed guidelines
specifically for patients with vasculitis.

On October 3, 2022, foreign scholars published a review in the authoritative journal Nat Rev Rheumatol (impact factor 32.
286), aiming to synthesize the recommendations of the above four expert groups and other literature, and provide comprehensive guidance
on reproductive health, pregnancy disease management and medication safety for vasculitis patients and clinicians.

Perigestational management of women with vasculitis

Monitoring during pregnancy

ACR guidelines recommend that a rheumatologist evaluate pregnant women at least every 3 months, with follow-up frequency varying
according to the patient's needs.
EULAR guidelines recommend risk assessment of placenta-associated pregnancy disorders such as pre-eclampsia and intrauterine growth restriction
by umbilical cord and uterine artery Doppler ultrasound at 20 to 24 weeks' gestation.
In addition, by measuring anti-Ro and aPL antibodies, doctors can stratify
patients according to their risk of pregnancy complications.
If the patient is positive for anti-Ro antibodies, ACR, EBCOG, and EULAR guidelines recommend fetal echocardiography at 18 to 24 weeks' gestation to assess for AV block
.
Hydroxychloroquine reduces the risk of neonatal lupus, including AV block, and ACR, EBCOG, and EULAR guidelines recommend hydroxychloroquine
for all pregnant women who are positive for anti-Ro antibodies.
Of note, the presentation of active vasculitis and pregnancy complications can overlap and needs to be differentiated
.

Medication management during pregnancy

A variety of treatments for vasculitis can be used during pregnancy, including azathioprine, colchicine, TNF inhibitors, cyclosporine, tacrolimus, and nonsteroidal anti-inflammatory drugs
.
Glucocorticoid therapy during pregnancy is considered safe, but its use
should still be minimized.
In addition, teratogens such as methotrexate, cyclophosphamide, and mycophenolate mofetil are best discontinued before pregnancy, and ACR guidelines recommend that patients should replace these teratogenic agents with pregnancy-compatible immunosuppressants
before pregnancy.

1.
Inactive vasculitis: Before pregnancy, pregnancy should be considered to start pregnancy compatible immunosuppressants or increase their dose to obtain or maintain vasculitic remission
.
Cyclic administration of rituximab maintains efficacy, and a single dose of rituximab prior to conception is an effective method
for controlling disease activity against neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV).
The ACR also recommends tapering the dose of glucocorticoids to <10 mg/day (prednisone or equivalent)<b22> if the patient's condition permits.
Maintenance doses of prednisone (≥10 to 20 mg/day) are associated with an increased risk of preterm birth in patients with systemic lupus erythematosus (odds ratio [OR] 3.
5).

2.
Active vasculitis: If the patient is suspected of having active vasculitis, especially pulmonary and/or renal vasculitis, it may be necessary to start glucocorticoids or increase their dose, and hormonal shock therapy
should be used in critical cases.
If the patient's condition permits, glucocorticoid replacement agents should be considered to reduce glucocorticoid doses
.
In addition, ACR guidelines conditionally recommend that patients with life-threatening or organ-threatening diseases such as glomerulonephritis or diffuse alveolar hemorrhage should be treated
with rituximab or cyclophosphamide.

3.
Hypertension during pregnancy: hypertension during pregnancy increases the risk of placental dysplasia, and according to ACOG guidelines, labetalol, hydralazine and nifedipine can be used to control blood pressure
during pregnancy.

4.
Pre-eclampsia: AOG, ACR, EULAR and EBCOG guidelines recommend that the following patients should use low-dose aspirin (usually 81-162mg) to prevent pre-eclampsia: a.
Have one or more pre-eclampsia risk factors: history of pre-eclampsia, multiple pregnancy, kidney disease, autoimmune disease, type 1 or type 2 diabetes and/or chronic hypertension; b.
Have more than one intermediate-risk factor: first pregnancy, age ≥ 35 years, body mass index [BMI] > 30kg/^m2, and/or family history
of pre-eclampsia.
Treatment should begin before 16 weeks' gestation and continue until delivery
.
The ACR guidelines also propose that patients with SLE and APS should use prophylactic aspirin to prevent pre-eclampsia
.

Vaccination during pregnancy

Vasculitis increases the risk of thrombosis, and patients should be evaluated before vaccination.

The ACOG guidelines recommend the following:

a.
HPV vaccine is not recommended during pregnancy, and can be given
before or after pregnancy.

b.
All pregnant women should be vaccinated against tetanus toxoid, attenuated diphtheria toxoid, and acellular pertussis (Tdap) within 27-36 weeks' gestation, as well as inactivated influenza vaccine
during influenza season.

c.
Pregnant women with lung disease or immunocompromised diseases (including vasculitis) may be considered for 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13).

d.
The measles-mumps-rubella (MMR) vaccine is a live attenuated vaccine that is contraindicated
during pregnancy.

e.
Clinicians should recommend additional vaccines
during pregnancy based on the patient's age, vaccination history, comorbidities, or risk factors for disease.

breastfeeding

ACOG recommends exclusive breastfeeding for the first 6 months after delivery to improve the newborn's immunity and nutrition, and recommends that it ideally last until the baby's first year of age
.
ACR guidelines recommend that all women with rheumatism choose breastfeeding
.

Reproductive health management in male vasculitis

Patients with vasculitis in men should be discontinued with cyclophosphamide and thalidomide before trying to conceive, while all other antirheumatic drugs are available
.
ACR strongly recommends that male patients undergo sperm cryopreservation prior to cyclophosphamide treatment to preserve fertility and do not use testosterone for combination therapy
while receiving cyclophosphamide.

summary

Patients with vasculitis should avoid conception while taking teratogenic medications and/or disease activity to reduce the risk
of preterm birth and fetal birth defects.
Patients should be followed up regularly during pregnancy to assess disease activity and the need for
escalation of treatment.
A variety of drugs used to treat vasculitis can be used during pregnancy, and in men with vasculitis, almost all antirheumatic drugs can be used
before pregnancy, except for cyclophosphamide and thalidomide, which should be discontinued before pregnancy.
Although the reproductive health management of patients with vasculitis is relatively complex, with the assistance of multidisciplinary teams and careful pregnancy planning, most patients achieve good pregnancy management and disease control
.

References: Sims C, Clowse MEB.
A comprehensive guide for managing the reproductive health of patients with vasculitis.
Nat Rev Rheumatol.
2022 Oct 3:1–13.
doi: 10.
1038/s41584-022-00842-z.
Epub ahead of print.
PMID: 36192559; PMCID: PMC9529165.