INTRODUCTION — Pregnancy may be complicated by new-onset or preexisting allergic disease, including rhinitis, urticaria, angioedema, or atopic dermatitis (AD). In contrast with asthma in pregnancy, relatively few studies have examined the management of other allergic disorders in pregnant persons.
This topic reviews the recognition and management of rhinitis, urticaria, angioedema, and AD in pregnancy as well as general principles of medication use during pregnancy. The diagnosis and management of asthma in pregnancy, anaphylaxis in pregnancy, the various dermatoses of pregnancy, and the management of allergic rhinitis in nonpregnant patients are discussed separately.
●(See "Anaphylaxis in pregnant women".)
●(See "Dermatoses of pregnancy".)
General approach to treating allergy in pregnancy — In any form of allergic disease, a primary element of management is avoidance of the culprit allergen when possible. Allergen avoidance is particularly important during pregnancy because the use of systemic medications should be minimized, if possible.
Females with significant allergic disease should ideally be evaluated before they become pregnant so that any skin testing, challenge procedures, or other exposures that might be necessary for definitive diagnosis can be safely performed. This is especially important for females with the following:
●Allergies to medications that may be needed during pregnancy, such as local anesthetics or drugs used in general anesthesia. (See "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions".)
●Allergies for which there are definitive treatments, such as stinging insect venom (yellow jackets, bees, fire ants, others). Some patients with these allergies are candidates for venom immunotherapy, which can be continued during pregnancy but should not generally be initiated in a patient who is already pregnant. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Pregnant women'.)
●Any female who has experienced anaphylaxis. Anaphylaxis can be devastating to both the mother and fetus. As a result, it is imperative to prevent a recurrence during pregnancy. (See "Anaphylaxis in pregnant women".)
Systems for assessing drug safety in pregnancy — When considering the use of medications in a pregnant person, the potential risk of a drug must be balanced against the effects of untreated disease. Despite the potential for harm, few drugs have been proven harmful in pregnancy, and fewer than 1 percent of congenital malformations can be attributed to drugs . However, statistical and ethical considerations make it unlikely that any drug will ever be "proven safe." A general discussion of the assessment of the risk of medication use based upon animal and human studies is discussed in more detail separately. (See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Safety of selected common medications used transiently in pregnancy'.)
Many allergic disorders can be managed with topical medications, including nasal sprays, eye drops, and topical lotions and creams. These preparations allow the drug to be concentrated at the site of inflammation so that less total drug is required to obtain clinical benefit. However, not all topical preparations are considered appropriate for use in pregnancy. (See 'Anaphylaxis' below and 'Rhinitis' below and 'Urticaria and angioedema' below and 'Atopic dermatitis' below.)
The US Food and Drug Administration (FDA) previously established five categories (A, B, C, D, and X) to describe a drug's potential for causing adverse effects during pregnancy and mandated that drugs introduced after 1980 be classified into one of these categories in the package insert . The categories are based upon the results of animal studies, human data, and consideration of whether the benefit of the drug's use during pregnancy outweighs the risk. In 2015, the FDA began overseeing the phase-out of pregnancy risk categories from prescription drug labeling and began requiring information from available human and animal studies of (1) known or potential maternal or fetal adverse reactions and (2) dose adjustments needed during pregnancy and the postpartum period. Additional information is available on the FDA website . A general discussion of the assessment of the risk of medication use based upon animal and human studies is discussed in more detail separately. (See "Management of asthma during pregnancy", section on 'Assessing drug safety in pregnancy'.)
In the interim, it is helpful for clinicians to be aware of the categories assigned to allergy medications within the older system. There are no allergy medications that meet the requirements for category A (adequately controlled studies show no risk). Most category B drugs are labeled as such because of reassuring animal studies without "adequate and controlled" human data. One may wish to choose a class B versus a class C drug (risk cannot be ruled out) among equally effective alternatives due to the reassuring animal studies.
ANAPHYLAXIS — Anaphylaxis is uncommon during pregnancy. However, it is important to recognize it rapidly and treat it effectively, as the maternal hypoxia and hypotension that can result may be catastrophic to both mother and fetus. Epinephrine is the treatment of choice in pregnancy. (See "Anaphylaxis in pregnant women".)
RHINITIS — Clinical experience suggests that the most common causes of nasal symptoms necessitating treatment during pregnancy are :
Other types of rhinitis are discussed separately. (See "An overview of rhinitis".)
Nondrug therapies — Nonpharmacologic interventions may be considered first in pregnant persons with rhinitis symptoms:
●Saline nasal sprays or nasal irrigation – Nasal irrigation is a nonpharmacologic intervention that is associated with improvement in a variety of rhinitis conditions and carries little risk if properly performed . A variety of devices, including bulb syringes and bottle sprayers, may be used to perform nasal lavage (table 1). Patients should use at least 200 mL in each nostril. This can be performed daily or only as needed for intermittent symptoms . In a randomized trial of pregnant persons, nasal saline irrigation was shown to be beneficial for treatment of allergic rhinitis .
●Exercise – Regular physical exercise can help by causing physiologic nasal vasoconstriction [8,9].
●Nasal dilator strips – Adhesive strips that mechanically hold the nasal valves open (external nasal dilators) are available over the counter and can be useful at night .
●Elevation of the head of the bed by 30 to 45 degrees – Placing bricks or other objects under the legs of the bed is more effective than using extra pillows .
Pregnancy rhinitis — Pregnancy normally induces hyperemia and edema of the nasal mucosa. This and other pregnancy-related changes in the upper respiratory tract are reviewed separately. (See "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes", section on 'Physiologic pulmonary changes in pregnancy'.)
Twenty to 30 percent of pregnant persons develop symptomatic nasal congestion during pregnancy, a condition called pregnancy rhinitis (or rhinitis of pregnancy) [12,13]. Pregnancy rhinitis may be defined as nasal symptoms during pregnancy lasting six or more weeks without other signs of respiratory tract infection and with no known allergic cause, disappearing completely within two weeks after delivery . Patients complain of persistent nasal congestion, accompanied by watery or viscous clear nasal secretions . Nasal congestion can lead to mouth breathing at night and reduced quality of sleep. The other causes of rhinitis listed above must be excluded .
The pathophysiology of pregnancy rhinitis is not known. In the past, it was attributed to changes in estrogen and/or progesterone, although there is little specific evidence to support this assertion . Smoking and allergic sensitization to dust mites were identified as risk factors for the development of pregnancy rhinitis in one study . However, neither asthma nor hay fever is more common among females who develop pregnancy rhinitis.
Management — Pregnancy rhinitis does not usually require therapy nor does it respond well to medications. In those who seek specific treatment, nonpharmacologic measures are suggested. (See 'Nondrug therapies' above.)
Several medications have been studied in pregnancy rhinitis, although none have demonstrated clear efficacy:
●Intranasal glucocorticoid sprays were not beneficial for pregnancy rhinitis in a randomized trial of 53 females .
●Pseudoephedrine is also occasionally used for severe pregnancy rhinitis, although oral vasoconstrictors should be avoided in the first trimester and in females with hypertension. (See 'Decongestants' below.)
Effect of pregnancy on preexisting rhinitis — Preexisting rhinitis may worsen, improve, or remain unchanged during pregnancy . These trends are similar to those seen with asthma, and one study found concordance between the course of asthma and that of rhinitis during pregnancy . This suggests that mechanistic factors involved in both diseases may be similarly altered during pregnancy.
Data suggest that rhinitis does not directly affect pregnancy outcome . However, uncontrolled rhinitis can indirectly affect pregnancy by impacting gestational nutrition, sleep, or stress. In addition, uncontrolled rhinitis may be a cause of snoring, which may increase the risk of gestational hypertension, preeclampsia, and intrauterine growth retardation, although not all studies have confirmed this association [22-24].
Uncontrolled rhinitis may also predispose to sinusitis or exacerbate coexisting asthma during pregnancy. In a study of 218 pregnant women with asthma , the presence and severity of rhinitis was associated with the level of asthma control. Thus, appropriate management of rhinitis during pregnancy can help women avoid exposures to other medications, such as antibiotics and oral glucocorticoids.
Allergic rhinitis/conjunctivitis — Allergic rhinitis is usually preexisting, although it may develop or be recognized for the first time during pregnancy. Patients with allergic rhinitis often report prominent sneezing, nasal pruritus, and watery rhinorrhea, and some have concomitant ocular itching and irritation. Common triggers for allergic rhinitis include dust mites, animal danders, molds, and pollens. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis", section on 'Clinical manifestations'.)
The management of allergic conjunctivitis during pregnancy is reviewed separately. (See "Allergic conjunctivitis: Management", section on 'Pregnant patients'.)
Evaluation during pregnancy — Although allergy skin testing is considered extremely safe, there are rare, highly sensitive patients in whom skin testing can induce systemic allergic reactions. Thus, in vitro tests are preferred during pregnancy for identification of specific inhalant allergens to which a previously untested patient is sensitive.
In vitro tests for allergen-specific immunoglobulin (Ig)E are widely available, and the use of these tests in the diagnosis of allergic rhinitis is reviewed in detail elsewhere. Alternatively, therapy can be initiated empirically, even if the causative allergens are not known. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis", section on 'Serum tests for allergy'.)
Our approach — Our approach to the management of allergic rhinitis is described below and summarized in an algorithm (algorithm 1).
●Allergen avoidance (if the causative allergens are known) and nonpharmacologic therapies should be recommended initially and may be adequate for mild symptoms. (See 'Nondrug therapies' above.)
●For intermittent or mild symptoms despite non-drug measures, we consider a second-generation antihistamine as needed or regularly. Loratadine (10 mg once daily), cetirizine (10 mg once daily), and fexofenadine (180 mg once daily) all have reassuring safety data. Cromolyn sodium nasal spray is another option, although it requires frequent dosing. (See 'Oral antihistamines' below and 'Cromolyn sodium nasal spray' below.)
●For moderate-to-severe symptoms, based on human data, we favor budesonide, fluticasone, or mometasone nasal spray as an initial therapy and add a second-generation antihistamine for additional symptom control, if needed. (See 'Glucocorticoid nasal sprays' below.)
Medication choices — The various therapies for allergic rhinitis and their safety in pregnancy are reviewed in this section. Our approach is discussed above. (See 'Our approach' above.)
Cromolyn sodium nasal spray — Intranasal cromolyn sodium may be considered a first-line therapy for mild allergic rhinitis in pregnancy because of its excellent safety profile. Cromolyn sodium is minimally absorbed into the systemic circulation when applied to a mucosal surface . Three human studies of over 600 pregnancies, including first trimester use, failed to detect any increased risk for congenital defects with inhaled cromolyn sodium, although there are no safety data specific to nasal or ophthalmic preparations .
Dosing of intranasal cromolyn is one spray per nostril up to six times daily. The utility of cromolyn is limited by the need for frequent dosing and by lower efficacy compared with newer therapies. However, the safety of this therapy and its availability without a prescription (ie, over the counter) make it a reasonable initial choice for some patients.
Glucocorticoid nasal sprays — Intranasal glucocorticoids are highly effective for allergic rhinitis and are particularly helpful for alleviating nasal congestion and postnasal drip. Glucocorticoid sprays are the treatment of choice for moderate-to-severe allergic rhinitis during pregnancy (table 2). The lowest effective dose should be used during pregnancy.
The safety of glucocorticoid nasal sprays in pregnancy has been based on reassuring data from glucocorticoid inhalers for asthma , which deliver higher doses than nasal sprays. The overall safety of intranasal glucocorticoids in pregnancy was confirmed by a 2016 study of over 140,000 pregnant persons, of whom 2502 were exposed to these medications during the first trimester [29,30]. There was no increase in overall rates of major congenital malformations or spontaneous abortions among exposed patients. The only intranasal glucocorticoid for which there was a signal of potential concern was triamcinolone, which was associated with malformations of the respiratory system specifically (adjusted odds ratio [OR] 2.71, 95% CI 1.11-6.64). This was based upon a small number of cases: two cases of unspecified congenital malformations of the respiratory tract, one case of congenital malformations of the larynx, two cases of trachea and bronchus abnormalities, and one case of choanal atresia. Other agents were not associated with an excess of any specific abnormalities. Some clinicians choose budesonide if starting intranasal glucocorticoids for the first time during pregnancy, since it was classified as a category B drug in the previous US Food and Drug Administration (FDA) system, based on reassuring data on inhaled budesonide from the population-based Swedish Medical Birth Registry, whereas most of the other agents were category C . The 2016 study also provided reassuring data about use of intranasal fluticasone or mometasone in the first trimester, as these agents were more commonly used in the study population and were not associated with adverse outcomes [29,30]. (See 'Systems for assessing drug safety in pregnancy' above.)
Oral antihistamines — Oral antihistamines are less effective for the treatment of allergic rhinitis compared with intranasal glucocorticoids, particularly for the relief of nasal congestion and postnasal drip. Several studies have evaluated the safety of antihistamines during pregnancy [32-36]. Most pregnant persons who require antihistamines are most appropriately treated with a second-generation agent because these drugs are less sedating and have fewer cholinergic side effects compared with first-generation agents.
●Among second-generation antihistamines, loratadine (10 mg once daily) and cetirizine (10 mg once daily), may be considered the second-generation antihistamines of choice in pregnancy. There are reassuring human data for each of these drugs in a large number of pregnant patients, and they were rated category B . Levocetirizine is also a category B drug, but there are few published human data. Data on use of fexofenadine in pregnancy are also reassuring .
●First-generation agents are widely available, inexpensive, and can be useful on an as-needed basis and/or before bed. Among the first-generation agents, chlorpheniramine has been recommended as the first-generation antihistamine of choice for use during pregnancy because it has been used for decades, and animal and human data are reassuring . The dosing of chlorpheniramine is 4 mg every four to six hours. Sustained-release formulations are available (8 mg up to three times daily and 12 mg twice daily). Dosing should not exceed 24 mg per day.
Antihistamine nasal sprays — Human safety data are not available for azelastine or olopatadine nasal sprays, although animal studies are reassuring . Until more information is available, we would suggest avoiding these medications during pregnancy unless a patient was uniquely responsive to one of them prior to pregnancy.
Decongestants — Decongestants are vasoconstrictors that are available as both oral preparations and nasal sprays. It is not known whether or not this group of drugs crosses the placenta .
●Intranasal decongestants – Decongestant nasal sprays can be used very briefly (eg, three days or less) for temporary relief of severe nasal congestion during pregnancy. Some reassuring human data exist for intranasal oxymetazoline [39,40], although one study found possible associations between oxymetazoline or xylometazoline and several malformations . Patients should be warned about dependence with prolonged use. (See 'Rhinitis medicamentosa' below.)
●Oral decongestants – Oral decongestants are best avoided altogether during the first trimester because of an uncertain risk of several rare birth defects . Pseudoephedrine can be used in the second and third trimesters in females without hypertension.
•Pseudoephedrine – Pseudoephedrine is administered at a dose of 60 mg, given at a maximum frequency of four times daily, or 120 mg of the long-acting preparation given twice daily. Oral decongestants should generally be avoided during the first trimester, but during the second and third trimesters, pseudoephedrine is the decongestant of choice in females without hypertension . In the United States, increasing abuse of pseudoephedrine as a stimulant in athletics and in the illegal production of methamphetamines has led to limits of how much can be obtained over the counter, and patients must provide identification (eg, a driver's license) to purchase the drug.
A possible association between pseudoephedrine and gastroschisis (baseline incidence of 1 in 10,000 births) was found in two case-control studies [38,41]. Infant gastroschisis has also been reported with maternal phenylpropanolamine use , suggesting a possible drug class effect. Another abnormality associated with first-trimester pseudoephedrine use is limb reduction defects . However, reassuring data on pseudoephedrine also exist. A Swedish study prospectively examined the pregnancy outcomes of 2474 females who had reported use of oral decongestants (mostly phenylpropanolamine or pseudoephedrine) in early pregnancy and 1774 females who used these medications in later pregnancy . No teratogenic effects were detected in either group. In addition, the use of these medications in later pregnancy (after the first antenatal visit) was associated with lower rates of premature birth, low birth weight, small-for-date infants, and perinatal death, prompting the authors to hypothesize that rhinitis of pregnancy may be a sign of good placental function. Although these data are reassuring, they do not have adequate power to exclude an increased risk of congenital malformations due to maternal first trimester use of oral decongestants.
•Phenylephrine – Phenylephrine should be avoided in pregnancy because of uncertain efficacy and questionable safety. Phenylephrine is less effective than pseudoephedrine for the treatment of rhinitis symptoms and may not be superior to placebo at the 10 mg dose that is commonly available over the counter [45-47]. In addition, phenylephrine (unlike pseudoephedrine) has strong alpha-agonist properties, and uterine blood vessels selectively express alpha-adrenergic receptors . Therapeutic doses of phenylephrine were shown to reduce uterine blood flow substantially in animal models . Studies of congenital defects and phenylephrine exposure have identified an increased risk of endocardial cushion defect [38,50]. Despite its clear inferiority, phenylephrine had been increasingly used as a substitute for pseudoephedrine in many over-the-counter preparations in the United States because of the abuse potential of pseudoephedrine.
•Phenylpropanolamine – Phenylpropanolamine is no longer available in the United States and many other countries due to a proposed increased risk of stroke in young females, although it is available in some parts of the world without a prescription. Its use in pregnancy is discouraged. Infant gastroschisis has been reported with maternal phenylpropanolamine use as with pseudoephedrine .
Antihistamines and decongestants combined — Patients with allergic rhinitis who have prominent nasal congestion often report more relief with the combination of an antihistamine and pseudoephedrine than with either drug alone. However, since pseudoephedrine should be avoided in the first trimester, it is preferable to recommend glucocorticoid nasal sprays instead to such patients during pregnancy. Glucocorticoid sprays provide particularly effective relief of nasal congestion. Efficacy studies of these agents are reviewed separately. (See "Pharmacotherapy of allergic rhinitis", section on 'Glucocorticoid nasal sprays'.)
Montelukast — Montelukast is approved for the treatment of allergic rhinitis and has reassuring animal and human gestational safety data regarding congenital malformations [51-53]. However, it is not as effective as intranasal glucocorticoids  and should generally only be used during pregnancy for the treatment of allergic rhinitis in patients who have demonstrated substantial benefit before pregnancy or in patients with confirmed allergic rhinitis not controlled by intranasal glucocorticoids and antihistamines.
Herbal therapies — We suggest avoiding herbal therapies during pregnancy because, in the United States and most other countries, herbal medicines are minimally regulated and monitored for adverse events by national surveillance systems. Safety issues surrounding the use of herbal preparations are reviewed elsewhere. (See "Overview of herbal medicine and dietary supplements" and "Hepatotoxicity due to herbal medications and dietary supplements".)
Allergen immunotherapy — Subcutaneous allergen immunotherapy (SCIT) is not initiated during pregnancy due to the potential harm that could result if a systemic reaction or anaphylaxis were to occur. However, patients who were tolerating and deriving benefit from SCIT prior to pregnancy may continue it through pregnancy in many cases.
Considerations against beginning immunotherapy during pregnancy include the following:
●The propensity for systemic reactions in that patient is unknown.
●Systemic reactions are more likely during initiation of immunotherapy.
●Immunotherapy typically takes months to work, so the patient would not derive clinical benefit for most of the pregnancy anyway.
The continuation of SCIT during pregnancy appears to be safe, aside from the risk of systemic reactions. Two studies of 230 pregnancies in 171 women receiving inhalant allergen immunotherapy reported no increase in abortions, perinatal deaths, prematurity, toxemia, or congenital malformations in the treated patients in comparison with both a nontreated pregnant-allergic control group and to the general population [2,31].
Based on this information, it is recommended that SCIT be continued during pregnancy in patients already receiving it who also :
●Appear to be deriving benefit
●Are not prone to systemic reactions to the immunotherapy
●Are receiving a maintenance dose or at least a dose that appears to be therapeutic for that patient
The dose is not increased during pregnancy, and some clinicians reduce the dose slightly in an effort to lower the risk of a systemic reaction further. If a pregnant patient has a systemic reaction to immunotherapy, treatment should be discontinued.
A similar approach is suggested for the use of sublingual immunotherapy (SLIT) during pregnancy. One study of 185 pregnancies did not find an increase in pregnancy complications in patients receiving SLIT compared with the general population or controls . SLIT should not generally be initiated during pregnancy, but it can be continued if a patient is already receiving it and tolerating it well. (See "Sublingual immunotherapy for allergic rhinitis and conjunctivitis: SLIT-tablets".)
Rhinitis medicamentosa — Rhinitis medicamentosa refers to rhinitis symptoms resulting from application of topical agents to the nasal mucosa. The most common precipitant is over-the-counter decongestant nasal sprays containing oxymetazoline. This adverse effect can be avoided by limiting use of these sprays to fewer than three days. (See 'Decongestants' above.)
Several days of nasal decongestant use leads to rebound nasal congestion as the medication wears off, prompting patients to increase the dose in an effort to obtain relief of symptoms and establishing a vicious cycle of nasal congestion and escalating medication use. Rhinitis medicamentosa may complicate viral respiratory infections or various causes of chronic rhinitis for which patients may resort to decongestant sprays.
Treatment involves discontinuation of the nasal decongestant and, in most cases, concomitant treatment with intranasal glucocorticoids. Treatment options are reviewed in more detail elsewhere. (See "An overview of rhinitis", section on 'Nasal decongestant sprays'.)
Acute bacterial rhinosinusitis — One study found that acute bacterial rhinosinusitis was more common in pregnant than nonpregnant patients , although this was not confirmed in a large database study . In the latter, a total of 103,129 pregnant patients were included who had live births during or between 2001 and 2010 and were continuously enrolled for the years before, during, and after the pregnancies. The proportions of patients treated with antibiotics for acute upper respiratory infection, with any encounter for acute sinusitis and with antibiotic treatment for sinusitis, were all greater in the year before and the year after pregnancy than during pregnancy. Sinusitis may still occur during pregnancy, and a high index of suspicion must be maintained for sinusitis during pregnancy because many pregnant females with sinusitis lack classic clinical findings . The diagnosis and treatment of sinusitis in pregnancy is reviewed separately. (See "Approach to the pregnant patient with a respiratory infection", section on 'Acute sinusitis' and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis" and "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment".)
URTICARIA AND ANGIOEDEMA — Urticaria, with or without angioedema, may occur during pregnancy because of any of the causes defined in the nonpregnant state. (See "An overview of angioedema: Pathogenesis and causes" and "New-onset urticaria".)
Urticaria limited to pregnancy is rare, but affected patients may experience recurrences in subsequent pregnancies [59,60]. The pathogenesis of urticaria of pregnancy is unknown, although speculation includes allergic sensitization to endogenous hormones [61,62].
Diagnosis — The diagnosis of urticaria is largely based on the appearance of the lesions. The diagnosis of acute and chronic urticaria is reviewed in detail elsewhere. (See "New-onset urticaria" and "Chronic spontaneous urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history".)
Differential diagnosis — Urticaria during pregnancy must be differentiated from other disorders that can mimic urticaria, as well as several of the dermatoses of pregnancy . The differential diagnosis of urticaria (in any patient) is reviewed separately. (See "Chronic spontaneous urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Differential diagnosis'.)
The dermatoses of pregnancy that are most likely to be mistaken for simple urticaria are:
●Autoimmune progesterone dermatitis of pregnancy
●Pruritic urticarial papules and plaques of pregnancy (PUPPP), also known as polymorphic eruption of pregnancy (PEP)
●Other pruritic dermatoses of pregnancy, such as pemphigoid gestationis, prurigo of pregnancy, and cholestasis of pregnancy
Dermatologic conditions that affect pregnant persons are reviewed in more detail separately. (See "Maternal adaptations to pregnancy: Skin and related structures", section on 'Pruritus' and "Dermatoses of pregnancy".)
Autoimmune progesterone dermatitis of pregnancy — A distinctive syndrome termed "autoimmune progesterone dermatitis of pregnancy" is characterized by a papulopustular eruption, transient arthritis, peripheral and tissue eosinophilia, spontaneous abortion, and delayed hypersensitivity to intradermal aqueous progesterone .
Autoimmune progesterone urticaria occurs in nonparous females, usually 7 to 10 days premenstrually [64-68]. Progesterone-induced anaphylaxis has also been reported  and is part of the spectrum of progestogen hypersensitivity . (See "Progestogen hypersensitivity".)
Pruritic urticarial papules and plaques of pregnancy — Pruritic urticarial papules and plaques of pregnancy (PUPPP) is an urticarial, pruritic eruption that develops in and around the abdominal striae in about 0.5 percent of pregnancies (picture 1A-B). (See "Dermatoses of pregnancy", section on 'Polymorphic eruption of pregnancy'.)
Laryngopathia gravidarum — Laryngopathia gravidarum is a rare disorder that can mimic angioedema of the larynx. It is an acute or chronic noninfectious, mildly inflammatory process of the laryngeal tissues in multigravid patients . The pathogenesis remains speculative, but it may comprise several different entities. It has been attributed to an abnormal effect of pregnancy hormones on the laryngeal mucosa because of its rapid reduction after delivery.
The acute form occurs just before parturition, whereas the chronic form occurs earlier in pregnancy and may recur in subsequent pregnancies. Both forms spontaneously subside postpartum. Symptoms include:
●Progressive dyspnea (occasionally necessitating an artificial airway)
●Nonfebrile sore throat and odynophagia
●Elevated white blood cell count and erythrocyte sedimentation rate (40 to 60 mm/hour)
The larynx and frequently the epiglottis demonstrate patchy, localized edema and congestion, but the aryepiglottic folds, arytenoids, vestibular region, and true vocal cords are unaffected. Microscopically, the surface epithelium and mucus glands are normal, but the submucosa appears edematous, being infiltrated with lymphocytes and plasma cells.
Management — In patients with new-onset urticaria, identification and avoidance of offending agents or causes would ideally prevent urticaria or angioedema symptoms and obviate pharmacologic treatment. When symptomatic therapy is required, H1 antihistamines are recommended. Choice of agent is discussed above. (See 'Oral antihistamines' above.)
In patients with chronic urticaria (ie, recurrent urticaria that is present most days of the week for six weeks or longer), there are no identifiable triggers in most cases. Therapy begins with H1 antihistamines at standard doses, but it is not uncommon for patients to require higher doses (eg, cetirizine 20 mg twice daily) to control symptoms. Higher doses have not been specifically studied in pregnancy.
The pharmacologic therapy of chronic urticaria in pregnancy is reviewed separately. (See "Chronic spontaneous urticaria: Standard management and patient education", section on 'Pregnant or lactating women'.)
Severe flares of acute and chronic urticaria are usually controlled with oral prednisone, although oral glucocorticoids should be avoided during the first trimester, if possible. After that, prednisone is preferred over other oral glucocorticoid agents. The safety of prednisone in pregnancy is reviewed separately. Severe chronic urticaria can also be treated with omalizumab, which has reassuring animal studies and for which some reassuring human pregnancy data exist . (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Glucocorticoids' and "Anti-IgE therapy", section on 'Safety in pregnancy and lactation'.)
Dosing of prednisone in patients with chronic urticaria is reviewed elsewhere. (See "Chronic spontaneous urticaria: Standard management and patient education", section on 'Systemic glucocorticoids for short-term control'.)
ATOPIC DERMATITIS — As with other atopic disorders, atopic dermatitis (AD) may worsen, remain the same, or improve with pregnancy [73,74]. In one study, most of the women whose symptoms worsened during pregnancy reported this trend by the 20th week .
Diagnosis — Most pregnant persons with AD are aware of their disease before pregnancy, since AD typically has its onset in infancy or early childhood. The most important clinical features essential to making the diagnosis of AD are :
●Chronic or recurring course
●Typical-appearing rash and distribution
The diagnosis of AD in pregnant patients is the same as in nonpregnant patients. (See "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis".)
Differential diagnosis — AD during pregnancy must be differentiated from other pregnancy-related pruritic skin changes :
●Idiopathic pruritus (pruritus gravidarum) has its usual onset during the first trimester and only excoriations are seen. It may be caused by a functional hepatic disturbance induced by estrogens. (See "Maternal adaptations to pregnancy: Skin and related structures", section on 'Pruritus'.)
●Cholestasis of pregnancy is a disorder presenting with pruritus of the palms and soles, generally without primary skin lesions (ie, other than excoriations) . Elevation of serum bile acids triggers pruritus. Cholestasis of pregnancy is associated with an increased incidence of stillbirth, intrapartum fetal distress, and preterm labor, so it is important to make this diagnosis by assessing liver function in pregnant patients with unremitting pruritus and excoriations. (See "Intrahepatic cholestasis of pregnancy" and "Pruritus associated with cholestasis".)
●Prurigo of pregnancy occurs in the second or third trimesters and is an erythematous papular eruption with excoriations, primarily localized to the anterior abdomen (picture 2). The mechanism has not been determined.
●Pruritic folliculitis of pregnancy usually occurs during the third trimester and presents with follicular papules and pustules on the trunk, which spread to the arms and legs. It usually resolves before delivery. (See "Dermatoses of pregnancy".)
Treatment — Ideally, symptoms of AD should be optimally controlled before conception so that the medications can be tapered to the lowest effective dose in preparation for conception and early pregnancy.
Certain medications should be discontinued in advance of conception:
●Methotrexate for severe AD (used by either the female or male partner) should be discontinued at least three months prior to conception.
●Psoralens plus ultraviolet A (PUVA) should be stopped prior to conception, although a specific drug-free interval has not been established .
Emollients — Treatment of AD during pregnancy should emphasize avoidance of triggering factors and maximize the use of emollients. (See "Treatment of atopic dermatitis (eczema)".)
Oral antihistamines — Orally administered antihistamines should be used to control pruritus. Loratadine, cetirizine, fexofenadine, or chlorpheniramine are the preferred agents. Chlorpheniramine is sedating and can be helpful at bedtime. (See 'Oral antihistamines' above.)
Topical corticosteroids — Data on the safety of low- or moderate-potency topical corticosteroids during pregnancy are reassuring . In contrast, caution is warranted with potent or superpotent topical corticosteroids, as use of these, particularly in the third trimester, has been associated with low birth weight [78-80].
When a topical corticosteroid is required for AD, hydrocortisone (0.5 to 2.5%, twice daily until symptoms are controlled) is a good initial choice, as it has a low potential for adrenal suppression . Patients should be counseled to use stronger agents sparingly and only on those areas of the body that do not respond to weaker agents. There are no data upon which to recommend one particular medium-potency topical corticosteroid over another. If potent or superpotent topical corticosteroids are absolutely needed, the amount used should be kept to a minimum, and fetal growth should be monitored .
Studies of the safety of topical corticosteroids in pregnancy are reviewed in more detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Use during pregnancy or lactation'.)
Oral glucocorticoids — For patients not responding to low- or medium-potency topical corticosteroids, oral prednisone may be preferable to the use of significant amounts of more potent topical preparations. If possible, oral glucocorticoids should be avoided during the first trimester. After that, prednisone is preferred over other oral glucocorticoid agents. The safety of prednisone in pregnancy is reviewed separately. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Glucocorticoids'.)
Topical tacrolimus and pimecrolimus — Reports of pregnancies in patients taking oral tacrolimus for preservation of organ transplants have been generally reassuring , although data on these agents are limited. Until more information is available, we suggest avoiding tacrolimus and pimecrolimus during pregnancy.
Dupilumab — The biologic dupilumab, which binds to the alpha subunit of the interleukin (IL-)4 receptor to modulate both the IL-4 and IL-13 pathways, is effective in moderate-to-severe AD. However, although animal studies are reassuring, dupilumab use in human pregnancy has not been studied.
Treatment of bacterial superinfection — Infectious exacerbations of AD, generally secondary to Staphylococcus aureus, should be treated with penicillinase-resistant synthetic penicillins or erythromycin in patients who are allergic to penicillin. (See "Treatment of atopic dermatitis (eczema)".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Asthma and pregnancy (Beyond the Basics)" and "Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Allergic rhinitis (Beyond the Basics)" and "Patient education: Contact dermatitis (including latex dermatitis) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Females with significant allergic disease should ideally be evaluated before they become pregnant, so that any skin testing, challenge procedures, or other exposures that might be necessary for definitive diagnosis can be safely performed and a plan for management during pregnancy can be formulated. (See 'Introduction' above.)
●The management of anaphylaxis during pregnancy is discussed elsewhere. (See "Anaphylaxis in pregnant women".)
●Rhinitis is relatively common in pregnancy, and etiologies include pregnancy rhinitis, allergic rhinitis, sinusitis, and rhinitis medicamentosa. Nonpharmacologic measures, such as nasal saline irrigation, can be helpful in all forms of rhinitis and should be recommended initially. (See 'Rhinitis' above and 'Nondrug therapies' above.)
●Pregnancy rhinitis refers to nasal congestion and discharge lasting six weeks or more during pregnancy, in the absence of other causes of rhinitis, with resolution within two weeks of delivery. In most patients, pregnancy rhinitis can be managed with nonpharmacologic measures alone. (See 'Pregnancy rhinitis' above.)
●For pregnant patients with allergic rhinitis symptoms that have not responded sufficiently to nonpharmacologic measures, we suggest one or more of the following therapies (algorithm 1) (see 'Allergic rhinitis/conjunctivitis' above):
•We suggest avoiding oral decongestants in the first trimester of pregnancy and in any pregnant patient with hypertension (Grade 2C). After the first trimester, we counsel patients to limit their use of these to occasional relief of severe nasal congestion. Decongestant nasal sprays should only be used in a limited manner as well, since they may cause rebound congestion after a few days of use. Herbal therapies should also be avoided because they may not be regulated or monitored for contaminants.
●For pregnant patients with chronic urticaria, we suggest loratadine or cetirizine (Grade 2C). Higher-than-usual doses, although not specifically studied in pregnancy, may be required. Severe flares can be treated with oral prednisone, ideally after the first trimester. (See 'Urticaria and angioedema' above and "Chronic spontaneous urticaria: Standard management and patient education", section on 'Pregnant or lactating women'.)
●The management of atopic dermatitis (AD) during pregnancy should emphasize avoidance of triggering factors, maximal use of emollients, and oral antihistamines as needed to control pruritus. (See 'Atopic dermatitis' above.)
•Patients should be counseled to use moderate-potency topical corticosteroids sparingly and only on those areas of the body that do not respond to weaker agents.
•During pregnancy, limited courses of oral prednisone may be preferable to the use of significant amounts of more potent topical corticosteroids. However, oral glucocorticoids should be avoided during the first trimester if possible.
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