Practical approach to maculo-papular rash in pregnancy in family practice

Choi-Man Yan 忻財敏

HK Pract 2005;27:300-305

Summary

The family physician may encounter pregnant patients presenting with maculo-papular rashes. Pregnancy-specific dermatoses, like polymorphic eruption of pregnancy and prurigo of pregnancy, are itchy and long lasting but usually do not affect the foetus. On the other hand, the rash in various infections in pregnancies is short-lived, and may be associated with constitutional symptoms and the infective organisms may adversely affect the foetus. It is important that maternal infections be correctly diagnosed through detailed history taking, meticulous physical examination and appropriate investigations. Early referral to obstetricians is mandatory if maternal infection is confirmed so that foetal diagnosis may be timely performed. Further management will depend on the particular organism detected and the likelihood of the foetus being affected, and may include termination of pregnancy, foetal therapy or foetal surveillance.

摘要

家庭醫生也會遇見患有斑丘疹性皮疹的孕婦。妊娠特有的皮膚病，如妊娠期多形性疹和妊娠痺疹， 是瘙癢和持久的，它通常不會影響胎兒。雖然傳染病祇引起短暫性皮疹， 但它可能伴有其他令身體不適的症狀，而且病原或會損害胎兒成長。 因此透過詳盡病歷，仔細體檢及適當化驗為傳染病作出正確診斷至為重要。 一旦證實患上傳染病，孕婦應及早轉介產科醫生為胎兒進行適時診斷。 再按病原及胎兒受感染機會作進一步處理，其中包括終止懷孕、宮內胎兒治療，或對胎兒作出適當監察。

Introduction

Maculo-papular skin rash is a not an uncommon occurrence in pregnancy. Family physicians are likely to meet patients presenting with such problem in their daily practice. The term 胎毒, literally meaning foetal poison, is commonly used by layman to describe the various itchy skin rash associated with pregnancy.

Pregnancy-specific dermatoses are one category of the causes of maculo-papular rash. More importantly, the rash may be a manifestation of infection which may or may not affect the foetus. Besides, drugs should not be forgotten as a cause of rash in the pregnant patients.

With proper diagnosis, not all pregnant patients with maculo-papular rash in pregnancy need to be referred to the specialists.

Skin diseases of pregnancy

Polymorphic eruption of pregnancy

It is also called "toxaemic rash of pregnancy" and is the commonest dermatosis specific to pregnancy with an incidence of 1 in 130-300.¹ It occurs more commonly in primiparous women and in multiple pregnancies. The rash usually occurs in the third trimester and presents as pruritic urticarial papules and plaques on the abdomen with umbilical sparing, along striae and on the limbs.² It has no effect on the foetus and it resolves rapidly after delivery. Recuurence is rare. Topical steroid and antihistamines may be prescribed for the treatment of pruritus.

Prurigo of pregnancy

It occurs mostly in multiparous women with an incidence of 1 in 300-450 pregnancies.^1,3 The onset is in late second trimester. There are pruritic red or brown excoriated papules extensor surface of limbs and occasionally on the abdomen.⁴ The foetus is not affected. Though pruritus improves at delivery, the rash may persist for several months afterwards. Recurrence is common and the pathogenesis is associated with atopy.¹ Treatment is similar to polymorphic eruption of pregnancy.

Infections

Rubella

Rubella virus is a single-stranded RNA togavirus and the infection is spread by respiratory droplets. In Hong Kong only 1-2% of young adult females are susceptible because of the vaccination programme. Therefore, Rubella infection is rare in pregnancy. The incubation period is 14-21 days. The infectivity is high with a 90% household attack rate. The infectivity period is 7 days before to 10 days after onset of rash.⁵ The infection is often asymptomatic in children but adults are likely to develop symptoms though in about 25-50% it is subclinical.⁶ A prodrome is not always present but it consists of malaise and tender lymphadenopathy which affects the postauricular, posterior cervical and suboccipital nodes. The rash, which coincides with fever, headache and myalgia, begins on the face and scalp and spreads downwards over the next 3 days. The lesions are very small pink macules which may become papular and then desquamate. Arthritis of the fingers and wrists is common and may persists for 2 weeks.⁷

A four-fold increase in IgG titres between specimens taken during and after the rash is diagnostic. Rubella-specific IgM titre is generally demonstrable one week after the appearance of the rash and persists for at least one month, occasionally three months. The risk of intrauterine transmission is 90% before 11 weeks, 55% at 11-16 weeks and 45% after 16 weeks gestation. The greatest damage occurs in the first trimester with deafness, heart disease and cataract being the commonest complications of the Congenital Rubella Syndrome. The risk of adverse foetal outcome is 90% before 11 weeks, 20% at 11-16 weeks, minimal risk of deafness 16-20 weeks and no increased risk after 20 weeks gestation.⁵ Termination of pregnancy (TOP) is justified for infection before 16 weeks gestation. Previously, viral identification by culture of foetal specimen is so inaccurate that the decision of TOP depends on the timing of infection. Nowadays, prenatal diagnosis is by Polymerase Chain Reaction (PCR) techniques on amniotic fluid.⁸ After 18 weeks of gestation, there is nearly no risk for the foetus. Invasive prenatal procedures are not required and ultrasound surveillance is sufficient.⁹

Human Parvovirus B19

Human Parvovirus B19 is a single-stranded DNA virus. It belongs to the parvovirus genus of the family Parvoviridae, which comprises the smallest and the simplest of the known DNA viruses. It binds to an antigen of the P system blood group known as the P antigen, which is present on the surfaces of erythrocytes, erythroblasts, megakaryocytes, foetal liver and heart cells.¹⁰ The infection is spread by respiratory droplets and is more common in the winter and spring. About 40-50% of young adult females are susceptible. One infection occurs in 400 pregnancies and seroconversion of 1.5-13% per annum among susceptible women. Incubation period is 13-18 days. The infectivity is medium, 50% and the infectivity period lasts from 10 days before to day of onset of rash.⁵ After a few days of slight pyrexia, malaise and headache as a prodrome, the rash starts as red raised erythema over the cheeks followed by a symmetrical reticular papular eruption on the buttocks and extensor surfaces of the limbs.⁷ The rash may last for a week or two and a transient symmetrical arthritis may occur over the hands and knees in over half of the adult cases.¹¹ Most infected pregnant women are asymptomatic or they have mild non-specific manifestations.

The diagnosis is usually made serologically - IgM parvovirus antibodies appears 3 to 4 days after onset of the clinical illness and persist in the blood for 3 to 4 months. IgG antibodies persist indefinitely.

The risk of intrauterine transmission is as follows: 0% before 4 weeks, 15% at 5-16 weeks and 25-70% after 16 weeks, increasing with gestation. At gestation less than 20 weeks, there is 9% excess foetal loss and 3% hydrops foetalis of which about half would die.¹² Exposure in the first and early second trimester (before 20 weeks) is associated with the highest foetal loss rate, though still-birth may still occur in the third trimester.¹³ It is estimated human parvovirus B19 is responsible for 8-10% of cases of non-immune hydrops. Risk of developing hydrops is highest when infection occurs between 12 and 18 week.¹⁴ TOP is not recommended. If maternal infection is confirmed, the foetus should be followed by serial ultrasound scans for 12 weeks for the early detection of foetal hydrops. Once hydrops is detected, referral to a tertiary foetal medicine centre is prudent. Viral DNA amplification using PCR in foetal serum or placental tissue is the most useful diagnostic test.¹⁵ Conservative management and reassessment may be appropriate as mild hydrops and anaemia may resolve spontaneously.

Measles

The measles virus is an RNA virus of the paramyxovirus group and spread via respiratory droplets. Its incidence dropped dramatically since the introduction of vaccination programmes. The incubation period is 10-12 days. There follows a prodrome of fever, malaise, coryza and conjunctivitis which resolve within a few days. The rash begins on the fourth day as conspicuous red macules and papules on the face, behind the ears and on the upper part of the neck. It spreads to the trunk and limbs within 3 days. The initial lesions coalesce. Clearing occurs from the third day down the body, leaving behind a brown stain and resolves within 14 days of the height of the eruption.⁷ The diagnosis is made by a four-fold rise in antibody titres between the acute and convalescent sample. Infection in pregnancy can lead to foetal demise and preterm delivery but is not associated with congenital infection or abnormalities.¹⁶ Human normal immunoglobulin may not prevent measles but has been shown to attenuate the illness.⁵ However, there is no evidence that it prevents foetal demise or preterm delivery.

Epstein-Barr virus

Some 50% of young adults are susceptible to Epstein-Barr virus (EBV) and half of these infections will present with infectious mononucleosis (IM). In fact, IM is a common presentation of primary EBV and is characterized by generalized lynphadenopathy, fever, sore throat and typical haematological and serological findings, including the detection of heterophil antibody.⁵ A generalized maculopapular rash is an associated accompanying feature, particularly if ampicillin or a similar antibiotic has been taken.¹⁷ Primary EBV infection in pregnancy carries no specific risk to the foetus.¹⁸

Cytomegalovirus

Cytomegalovirus (CMV) can cause an IM-like syndrome with, rarely, a generalized maculopapular rash. Transmission usually occurs through close and intimate contact. The incubation period varies from 4 to 8 weeks. Primary infection with CMV may lead to intrauterine infection, where the risk of transmission is about 40%, yet the effects are difficult to predict and no effective intervention exists. The risk of congenital infection in recurrent infection is probably 1-2%.¹⁹ Maternal infection acquired in all trimesters has been associated with adverse outcome, the risk of neurological damage is probably greater when a primary infection occurs earlier in pregnancy. The risk of foetal damage in recurrent infection is probably lower.^20,21 Overall, 80-90% of children with congenital CMV infection will be neurologically and developmentally normal. Since 60% of women do not transmit CMV in utero and since the majority of infected neonates do not develop disease, the risk of a woman with primary infection having a baby damaged by congenital CMV is about 7%. Therefore, it is proposed that documented maternal primary infection on its own is not a sufficient criterion to recommend TOP.²²

PCR in addition to viral culture of amniotic fluid is the best diagnostic tool for the detection of vertical transmission in pregnancies affected by CMV. When these tests are negative and the gestational age is less than 21 weeks, amniocentesis should be performed later in pregnancy to reassure the patient since amniocentesis performed too early after infection may result in false-negative results.²³ For those who elect to continue their pregnancies, serial ultrasound scans are useful for assessment of foetal status.

Enterovirus

Enterovirus infection may also present with maculo-papular rash. It is not associated with any particular foetal consequence, though rarely it can result in miscarriage, as can any febrile illness.²⁴

Toxoplasmosis

The majority of acute toxoplasmosis is either asymptomatic or associated with a mild non-specific illness. Occasionally, it may present as IM-like syndrome. It is very rare in Hong Kong. The incidence of acute infection in pregnancy and the rate of intrauterine transmission is not well established. Besides, the proportion of children with congenital toxoplasmosis developing disease, as well as the degree of handicap suffered, is not clear.^25,26 Moreover, the diagnostic tests for foetal infection have suboptimal specificity, resulting in possibly unnecessary therapeutic interventions, the efficacy of which remains uncertain due to the lack of properly controlled, randomized prospective studies.²⁷ Thus, the management options of confirmed maternal infection may include termination of pregnancy or foetal surveillance by ultrasonography to look for evidence of foetal infection.

Secondary Syphilis

Features of secondary syphilis include generalized lymphadenopthy and a maculopapular rash which may involve palms and soles. Both the Venereal diseases research laboratory (VDRL) test and Fluorescent treponemal antibody-absorbed (FTA-ABS) test will be positive. Treatment with procaine penicillin prevents most cases of congenital syphilis when given early in pregnancy.²⁸

Drug rashes

Allergic rashes may occur to antibiotics which are not uncommonly prescribed for urinary tract infection and upper respiratory tract infection. In addition, some of the Chinese population has the habit of taking herbal medicine as a tonic - even in pregnancy.

Approach to maculo-papular rashes in pregnancy

A history of taking drugs may be obvious. A history of constitutional symptoms in addition to short-lived rash points more to infection while long-lasting pruritic rashes usually point towards the common dermatological changes associated with pregnancy.

In the face of infective rashes, especially in the first half of pregnancy, detailed history should be taken. Any history and evidence of vaccination and past infection should be documented. (Table 1) Physical examination is obviously important since measles and syphilitic rashes may be characteristic and generalized lymphadenopathy may be detected in EBV, CMV and secondary syphilis. (Table 2)

Apart from performing an infection screening, including serology for Rubella virus, Human Parvovirus, CMV and toxoplasma gondii, and syphilis, booking serum is usually available for comparing with the current serology. Paired serology should always be done. Referral to obstetricians should be made in case of sero-conversion, recurrent CMV infection or a reactive test for syphilis. (Table 3)

Prenatal diagnostic procedures may be employed to ascertain whether a foetus has been infected though an infected foetus is not necessarily an affected one. Micro-organism may be detected in amniotic fluid or chorionic villi by culture. However, cell culture is slow and labour-intensive and is less sensitive than molecular amplification techniques.²⁹ Diagnosis may also be achieved through PCR to detect viral nucleic acid or electronic microscopy to visualize the viral particle. The finding of IgM in foetal blood obtained by cordocentesis implies a foetal response to infection. However, IgM is usually not produced by the foetus till 22^th week of gestation.

Amniocentesis carries a low risk of post-procedure foetal loss and morbidity. It has the lowest risk of introducing a microorganism into a previously uninfected foetus and should therefore be the standard invasive procedure used for the diagnosis of congenital infection. Delays of at least 7 weeks between the serological diagnosis of maternal CMV infection and the invasive procedure is recommended to increase the sensitivity of prenatal diagnosis.³⁰

Subsequent management will depend on the particular organism identified and whether foetal infection is present or not and may include termination of pregnancy, foetal therapy or foetal surveillance by ultrasonography. Foetal surveillance of pregnancies at risk of foetal infection is by means of serial ultrasound examinations carried out two-weekly till delivery. Foetal hydrops, brain abnormalities and hyperechogenic lesions are the most common ultrasound markers of a congenital infection.³¹

Conclusion

The family physician may encounter pregnant patients presenting with maculo-papular rash. Pregnancy-specific dermatoses are easy to diagnose because they are itchy and long-lasting. Infection in pregnant women, on the other hand, is short-lived and may be associated with other symptoms.

The most important diseases to diagnose, especially in early pregnancy, are rubella and human parvovirus infection since timely diagnosis will affect the subsequent management. Other viral diseases will either not affect the pregnancy or no specific management can be offered because of the unpredictability in outcome. Early referral to the obstetricians should be made if maternal infection is confirmed so that foetal assessment may be performed. Further management will depend on the particular organism detected and the likelihood of the foetus being affected.

Key messages

1. Polymorphic eruption and prurigo of pregnancy may present as pruritic and long-lasting maculo-papular rash and usually do not affect the foetus.
2. Short-lived maculo-papular rash with constitutional symptoms may point towards infections which may affect the foetus.
3. Drug history is important.
4. The morphology and distribution of the rash and any lymphadenectomy should be noted.
5. Investigations should include serology of Rubella virus, Human Parvovirus B19, Cytomegalovirus, toxoplasma gondii and syphilis.
6. Early referral to obstetricians is mandatory if maternal infection is confirmed so that foetal diagnosis may be timely carried out.