Pregnancy Associated Skin Changes Among

PREGNANCY ASSOCIATED SKIN CHANGES AMONG

PRIMIGRAVIDAE ATTENDING ANTENATAL CLINIC AT OBAFEMI

AWOLOWO UNIVERSITY TEACHING HOSPITALS COMPLEX, ILE-

IFE, OSUN STATE, NIGERIA.

A DISSERTATION SUBMITTED TO THE NATIONAL

POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PARTIAL

FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF THE

FELLOWSHIP OF THE COLLEGE IN INTERNAL MEDICINE:

SUBSPECIALITY: DERMATOLOGY.

1. Name of Candidate: Dr. Olanrewaju Fatai Olatunde,

MBBS (Maiduguri), 2001.

(08035765004, [email protected])

2. Number of Candidate: AF/009/10/005/719

3. Faculty of Candidate: Internal Medicine

DECLARATION

I hereby humbly declare that the writing and execution of the study contained in this dissertation was carried out by me and it is original and has never been presented to any other College for

Fellowship, nor has it been submitted elsewhere for publication.

Signature:……………………. Date:………………………..

Dr Olanrewaju Fatai Olatunde

SUPERVISION

This study was carried out under our supervision at OAUTHC, Ile-Ife, Osun State, Nigeria.

NAME OF SUPERVISORS

1. PROF. O. ONAYEMI

CONSULTANT, DERMATOLOGY/VENEREOLOGY

OAUTHC, ILE-IFE, OSUN STATE.

Signature:…………………………………...

Date: ………………………………………..

2. PROF. (MRS).O.A. OLASODE

CONSULTANT, DERMATOLOGY/VENEREOLOGY

OAUTHC, ILE-IFE, OSUN STATE.

Signature……………………………………

Date: ………………………………………..

3. DR. A.B. ADEYEMI

CONSULTANT, OBSTETRIC/GYNAECOLOGY,

OAUTHC, ILE-IFE, OSUN STATE.

Signature:……………………………………

Date: …………………………………………

HEAD OF DEPARTMENT’S CERTIFICATION

I hereby certify that the writing and execution of the study contained in this dissertation was carried out by Dr. Olanrewaju Fatai Olatunde under the supervision of Prof. O. Onayemi,

Prof. (Mrs) O.A. Olasode, and Dr A.B. Adeyemi.

Signature:……………………………….

Professor A.B. Kolawole,

Department of Medicine,

Obafemi Awolowo University Teaching Hospitals Complex,

Ile-Ife, Osun state.

TABLE OF CONTENTS TITLE PAGE i DECLARATION ii SUPERVISION iii HOD’S CERTIFICATION iv TABLE OF CONTENTS v DEDICATION vi ACKNOWLEDGEMENTS vii LIST OF TABLES viii LIST OF FIGURES ix KEY OF ABBREVIATIONS x SUMMARY xi CHAPTER ONE: INTRODUCTION 1 CHAPTER TWO: LITERATURE REVIEW 3 CHAPTER THREE: AIMS AND OBJECTIVES OF THE STUDY 23 CHAPTER FOUR: JUSTIFICATION OF THE STUDY 24 CHAPTER FIVE: SUBJECT, MATERIALS AND METHODS 25 CHAPTER SIX: RESULTS 31 CHAPTER SEVEN: DISCUSSION 54 CHAPTER EIGHT: CONCLUSION AND RECOMMENDATIONS 65

REFERENCES 66 APPENDICES I. PROFORMA 77

II. INFORMED CONSENT FORM 84

III. ETHICAL APPROVAL 85

ACKNOWLEDGEMENTS

Glory is to God Almighty, my Strength in ages past, my present day help and our hope for the future.

I am indeed very grateful for the mentorship and experience gathered from my great teachers of Dermatology- Prof. O. Onayemi and Prof. (Mrs.) O.A. Olasode. I want to also appreciate them for their immense support and contribution towards the success of this study.

My special thanks for the support and encouragement I received from Dr A.B. Adeyemi,

Consultant Obstetrician/Gynaecologist who allowed me to carry out this study on his patients and accepted to be a co-supervisor.

My gratitude also goes to my Head of Department, Prof. B.A. Kolawole for his words of encouragement, great support, simple and exemplary lifestyle he impacted into my life during the period of my residency training. My sincere gratitude goes to Dr. (Mrs.) O.A. Oninla,

Consultant Dermatologist, her advice and teachings were of immeasurable value.

I must also thank all consultants and residents in the Departments of Medicine and

Obstetrics/Gynaecology of Obafemi Awolowo University Teaching Hospital, Ile-Ife.

I wish to express my sincerest gratitude to Dr O.I. Ezejiofor and Dr (Mrs) O. Oke, both

Consultant Dermatologists, for their support and the time they spared reading through and correcting this work. To all the resident doctors in the Department of Dermatology especially Dr

M.M. Oripelaye and Dr (Mrs.) H. Bello, I am greatly indebted to you for your support and contribution towards this study.

My special appreciation and praise to the Lord Jesus, my Redeemer, Who led me through this tough path particularly during my several trips from Owo, Ondo State to Ile-Ife, Osun State.

LIST OF TABLES

TABLE 1: Socio-demographic characteristic of the Subjects and Controls

TABLE 2: General prevalence of pregnancy associated skin changes among subjects.

TABLE 3: Prevalence of the three classes of pregnancy associated skin changes in

subjects and controls.

TABLE 4: Prevalence of the subclasses of pregnancy associated skin changes in

subjects and controls

TABLE 5a: Prevalence and pattern of pigmentary physiological) skin changes in

pregnant subjects and controls.

TABLE 5b: Prevalence and pattern of other physiological skin changes in

pregnancy and controls.

TABLE 6: Prevalence and pattern of some other dermatoses in pregnancy and

controls.

TABLE 7: Prevalence and pattern of clinical presentation of acne vulgaris in

pregnancy.

TABLE 8a: Association between some skin changes in pregnancy and gestational age.

TABLE 8b: Association between some other skin changes in pregnancy and gestational

age.

LIST OF FIGURES Figure 1: General prevalence of pregnancy associated skin changes among subjects and controls.

Figure 2: Shows the trimester distribution of subjects recruited into the study.

Figure 3: Pattern of distribution of striae gravidarum in pregnant subjects.

Figure 4: Clinical pattern of melasma in pregnancy and control.

Figure 5: Prevalence and pattern of anatomical sites of pruritus in pregnancy.

Figure 6: Hirsutism on the abdomen.

Figure 7: Hirsutism on the chin.

Figure 8: Linea nigra.

Figure 9: Scar hyperpigmentation on the abdomen.

Figure 10a: Voigt’s lines on the posteriomedial thigh.

Figure 10b: Voigt’s lines on the posteriomedial thigh.

Figure 11: Nipple, areola and breast hyperpigmentation.

Figure 12: Increased naevus pigmentation on the right arm.

Figure 13: Skin tags on the neck area.

Figure 14: Striae gravidarum on the abdomen.

Figure 15: Palmar erythema at the tip of the fingers.

Figure 16: Melanonychia of the 2nd, 3rd and 4th finger nails.

Figure 17: Bilateral pedal oedema.

Figure 18: Leg varicosity on the leg.

Figure 19: Pityriasis versicolor on the abdomen.

Figure 20: Acne vulgaris on the face.

KEYS TO ABBREVIATIONS

AD - Atopic Dermatitis

ACTH- Adrenocorticotrophic hormone

AEP - Atopic Eruption of Pregnancy

AN - Acanthosis Nigricans

BMI - Body Mass Index

BMZ - Basement Membrane Zone

BSA - Body Surface Area

EGA- Estimated Gestational Age

HIV - Human Immunodeficiency Virus

HSV - Herpes Simplex Virus

ICP - Intrahepatic Cholestasis of Pregnancy

LMP - Last Menstrual Period

MSH - Melanocyte Stimulating Hormone

PDL - Pigmentary Demarcation Line

PEP - Polymorphic Eruption of Pregnancy

PG - Pemphigoid Gestationis

PSP - Pregnancy Specific Dermatosis

PT - Pregnancy Test

PV - Pityriasis Versicolor

USS - Ultrasound Scanning

VZV - Varicella Zoster Virus

SUMMARY

BACKGROUND.

The skin is the largest organ in the human body and it undergoes significant changes during pregnancy just like other systems such as endocrine, immune, metabolic and vascular systems.

These pregnancy associated skin changes are neglected aspect of obstetric care despite the skin being of great cosmetic concern to the pregnant woman.

These skin changes could be physiological or pathological. Pregnancy associated skin changes has been broadly classify into three which are; Physiological, Some dermatoses affected by pregnancy and Pregnancy specific dermatoses. While physiological skin changes cause cosmetic anxiety to the pregnant women, some of the pregnancy specific dermatoses can pose risk to the unborn baby and the mother. The pathogenesis of these skin changes has been attributed to physical factors, genetic factors and rise in levels of ovarian, placental and pituitary hormones during pregnancy. Documenting the prevalence and pattern of pregnancy associated skin changes in this environment was the subject of this research.

AIMS AND OBJECTIVES

The specific objectives are to determine the prevalence of skin changes among primigravidae, to document the clinical pattern of the skin changes and to correlate the documented skin changes with gestational age.

METHODOLOGY

The study was a descriptive cross-sectional observational study. Study location was the

Department of Obstetrics and Gynaecology, Obafemi Awolowo University Teaching Hospitals

Complex OAUTHC), Ile-Ife. Clearance was obtained from Ethics and Research Committee

10 before the patients were recruited. Patients were selected consecutively after informed consent had been obtained. Two hundred and forty subjects and 240 controls were appropriately recruited into the study. A structured questionnaire was used to collect essential information from each participant. Physical examination of the skin, hair and nail was done in a well lit room and with magnify lens where necessary.

RESULTS

The mean ages of the participants were 27.53±3.88 years for subjects and 27.50±4.1 years for controls. The prevalence of pregnancy associated skin changes varied between trimesters and increased as pregnancy advanced. The general prevalence in this study were 88.3 n=212) in the first trimester, 98.3 n=236) each in the second and third trimesters compared to 47.5

n=114) in controls. In some pregnant women, more than one type of skin changes were seen.

Physiological skin changes ranked highest with a prevalence of 77.1 n=185) in the first trimester, 95.0 n=228) in the second trimester and 94.6 n=227) in the third trimester while only 44.6 n=107) of similar skin changes were seen in controls. Pigmentary changes were the commonest physiological changes noticed in this study and mucous membrane changes was the least with a prevalence of 1.3 n=3) in the first trimester, 2.1 n=5) in second trimester and

1.7 n=4) in third trimester. Other physiological skin changes seen in this study were glandular, nail, connective tissue, hair and vascular. Other dermatoses affected by pregnancy such as atopic dermatitis, vaginal candidiasis, pityriasis versicolor, skin tag, pruritus) were seen in 33.3

n=80), 36.7 n=88) and 50.4 n=121) in first, second and third trimesters respectively. No case of pregnancy specific dermatoses such as atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis and intrahepatic cholestasis of pregnancy) was

11 seen in the course of the study supporting the rarity of the disease as documented in previous studies.108, 112

Among the possible determinants of presence of skin changes in pregnancy were hormonal

(pituitary, ovarian, placental) factors, genetic factors, environmental factor, gestational age, and skin colours.

CONCLUSION

The high prevalence rate of skin changes in pregnancy documented in this study especially physiological skin changes is therefore consistent with the findings by other workers from the other parts of the world.16,17 Some of these skin changes were statistically significant with increasing gestational age.

CHAPTER ONE

INTRODUCTION

Pregnancy is a physiological and transient period where medical intervention is usually not required or at least is restricted to checking expected events.1 Pregnancy affects virtually all body systems with the main changes occurring in the endocrine, immune, metabolic and vascular systems.2 These changes are aimed at sustaining and enabling normal growth and development of the fetus. The skin is no exception to these changes. The skin changes could be physiological or pathological.3

The majority of physiological skin conditions related to gestation resolve after childbirth,4 and they usually return to pre-pregnancy status within six weeks post-partum.5

These physiological cutaneous changes serve as markers of pregnancy and are generally benign, however they may cause significant concern or cosmetic distress for the pregnant woman. Rarer and of more concern are the specific dermatoses of pregnancy which are pathological skin eruptions unique to gestation.4 The rarity of these specific dermatoses of pregnancy, their variable clinical morphology, the lack of unequivocal diagnostic criteria as well as limited treatment options have led to confusing terminologies and have made their management difficult over decades.6 Conflicting and overlapping nomenclatures have added to the confusion.7 Until recently, most of these skin changes in pregnancy were poorly characterized and understood. There is also a significant overlap between their clinical and histopathological features and these features are helpful in supporting the diagnosis4.

Recently, the contribution of studies in histopathology, immunoflourescence, immunogenetics, and molecular biology has helped in elucidating the nature of some of the

13 dermatoses. This has led to better understanding of the pathogenesis of some of the dermatoses of pregnancy.

A number of complications can result from the skin changes in pregnancy. While physiological changes cause cosmetic anxiety to the pregnant women, the pregnancy specific dermatoses like intrahepatic cholestasis of pregnancy (ICP) can pose increased risk of fetal distress, prematurity and still birth.8 Potential fetal and maternal risk in this regards must be discussed with the pregnant women. A team approach that involves Dermatologist,

Paediatrician, Obstetrician and Gastroenterologist is the optimal way to treat the potential maternal, fetal and neonatal complications of the dermatoses.9

Skin changes in pregnancy, a neglected aspect of obstetric care, has not been extensively studied in this environment. This has led to dearth of adequate information about the magnitude of the problem in Nigeria and Africa. Most of the studies available are from the

Caucasians and Asians population. This work is therefore aimed at documenting the epidemiologic characteristics of these pregnancy associated skin changes among primigravidae attending Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife,

Nigeria and to stimulate more research in this field.

CHAPTER TWO

LITERATURE REVIEW

HISTORICAL BACKGROUND

Von Hebra was the first person to show interest in skin changes during pregnancy when he introduced the concept of dermatoses of pregnancy in 187210,11 and coined the term impetigo herpetiformis.

Milton in the same year described the first specific dermatosis of pregnancy under the name herpes gestationis12 now known as pemphigoid gestationis to distinguish it from herpes infections.

In 1904, Besnier described another pregnancy related skin disease which he termed prurigo gestationis.13 Costello (1941) employed this term and designated all pregnancy-related dermatoses which were not herpes gestationis as prurigo gestationis of Besnier.6

Kroumpouizos et al14 in 2001 simplified the skin changes in pregnancy into the present three categories to include: physiological skin changes in pregnancy, dermatoses affected by pregnancy, and pregnancy specific dermatoses.

Several authors have also described many pregnancy dermatoses under different names.

It was only after the introduction of histopathology, immunoflorescence microscopy, immunogenetic and molecular biology that many were characterized.15

EPIDEMIOLOGIC PATTERN OF SKIN CHANGES IN PREGNANCY

The cutaneous changes in pregnancy vary widely in their prevalence and aetiopathogenesis. Kumari et al16 reported the prevalence of physiological cutaneous changes to be

100% among the 607 pregnant women studied in Southern India. The most common physiological changes identified were pigmentary alterations which were found in 91.4% of the pregnant women. In the same study, the prevalence of specific dermatoses was observed to be 3.6% and that of other dermatoses affected by pregnancy to be 20.6%.16 In another study involving 2000 pregnant women in a tertiary hospital in India, the prevalence of physiological skin changes was 87.88%.17

Chander et al18 in Northern India studied 1430 pregnant women and observed that 5% of them had specific dermatoses of pregnancy while Masood et al3 in Pakistan study put it at 6.5%.

The possible reasons for discrepancies in prevalence of cutaneous changes in pregnancy could be due to skin phototypes and racial differences.17

CLASSIFICATION OF SKIN CHANGES IN PREGNANCY

The classification of dermatoses of pregnancy has been controversial for a long time.14

Shornick proposed classification of physiologic skin changes in pregnancy to include changes in pigmentation, alterations of the connective tissue, vascular system, and endocrine function as well as changes in hair and nails.20

Pregnancy is also known to influence the course of pre-existing skin diseases in both positive and negative ways. For example psoriasis is known to improve during pregnancy while acne gravidarum gets worse.21

The first simplified classification of specific dermatoses of pregnancy was presented by

Holmes et al in 1982 and included pemphigoid gestationis, polymorphic eruption of pregnancy

16 and prurigo of pregnancy.22 Shornick in 1998 further introduced intrahepatic cholestasis of pregnancy into the classification of specific dermatoses of pregnancy.20 Ambros-Rudolph et al. added atopic eruption of pregnancy to the classification.23

Kroumpouizos et al14 later suggested a more simplified classification of these dermatoses into three categories: physiological skin changes in pregnancy, dermatoses affected by pregnancy, and pregnancy specific dermatoses.

ADAPTED SIMPLIFIED CLASSIFICATION OF DERMATOSES IN

PREGNANCY BY KROUMPOUIZOS et al14

1. Physiologic skin changes in pregnancy

a. Pigmentary (Hyperpigmentation, melasma).

b. Hair (Hirsutism, male-pattern alopecia).

c. Nail (increased nail growth, melanonychia, nail fragility).

d. Glandular ( eccrine function, apocrine function, sebaceous gland )

e. Connective tissue (striae gravidarum)

f. Vascular (palmar erythema, non-pitting oedema, varicosity )

g. Mucous membrane (gingivitis).

2. Some dermatoses affected by pregnancy

a. Inflammatory disorders (atopic dermatitis, Psoriasis)

b. Infections (candidiasis, pityriasis versicolor, Dermatophytes, Herpes virus, warts)

c. Tumours (pyogenic granuloma, skin tags)

d. Miscellaneous (pruritus, acanthosis nigricans)

3. Pregnancy Specific Dermatoses (PSPs)

a. Atopic eruption of pregnancy (AEP)

b. Polymorphic eruption of pregnancy (PEP)

c. Pemphigoid gestationis (PG)

d. Intrahepatic cholestasis of pregnancy (ICP)

SKIN CHANGES IN PREGNANCY AND THEIR PATHOGENESIS

1. PHYSIOLOGICAL SKIN CHANGES IN PREGNANCY

A. PIGMENTARY CHANGES IN PREGNANCY

I. Hyperpigmentation

This is the most significant physiological skin change that occurs during pregnancy. As many as 90% of pregnant patients experience some form of hyperpigmentation, usually in discrete areas or pattern.24 In a study of 607 pregnant women by Kumari et al., most common physiological changes in pregnancy were pigmentary alterations seen in 91.4% (555 cases).16

Shah et al in another study reported the prevalence of pregnancy induced hyperpigmentation to be 87.3%.25 In a related study of 2000 pregnant women in India, Rathore et al reported pigmentary changes in 85.9% of the patients.17 The physiology of hyperpigmentation may be related to elevated serum levels of melanocyte-stimulating hormone (MSH), oestrogen and possibly progesterone.26-28 The majority of these physiology skin conditions resolve after childbirth within six weeks postpartum.4 They can present with generalized or localized hyperpigmentations such as linea nigra or pigmentary demarcation lines.

a. Generalized hyperpigmentation

Hyperpigmentation begins early in the first trimester of pregnancy, and is one of the earliest signs of pregnancy, and it continues until delivery. Mild generalised hyperpigmentation

18 is usually seen with accentuation of normally hyperpigmented areas such as the areola, nipples, genital skin, axillae, breast, nevi, freckles, inner thigh.14 The other sites of increased localized pigmentation are seen over the abdomen, linea nigra, face, buttocks, scar pigmentation, breast and neck.16

b. Linea nigra

Linea nigra is the darkening of the linea alba.14 Linea nigra extends from the suprapubic area to the umbilicus.29 Kumari et al,16 studied 607 pregnant women in India and reported that linea nigra was the most common pigmentary change which was found in 91.4% of cases.16

Similarly, George et al29 reported that pregnant women more often have linea nigra than non- pregnant women of the same age. Their findings suggested that the likelihood of having a linea nigra depends on the level of sex hormones,29 and distribution of melanocytes at the linea alba.

c. Pigmentary demarcation lines

Pigmentary Demarcation Lines (PDLs) also known as Voigt’s lines or Futcher’s lines,30 are physiological abrupt transition lines from area of deeper pigmentation to the area with less pigmentation.30 These have been described most often in the skin of African and Japanese.30

Eight different types of PDLs (A-H) have been classified according to locations. PDLs typically present as type B during pregnancy31 (posterior-medial portion of the lower extremities). An association with type A lines is possible but not frequently seen.31 Kumari et al reported one case with type B PDL of the 607 pregnant women studied in India.16 Another report describes four cases in Puerto Rican women developing demarcation lines; all of them developed the condition only during pregnancy, with complete disappearance between the first and third months

19 postpartum.32 The pathogenesis of type B pigmentary demarcation lines is largely unknown.33

The explanation for this phenomenon was compression of peripheral nerves by the enlarged uterus in the late period of pregnancy, thus influencing the innervated cutaneous microvasculature to induce neurogenic inflammation with resultant pigmentation.34 Other authors have hypothesized that mosaicism causes the pigmentary abnormality.35

Types of pigmentary demarcation lines

TYPES SITE

A Anterolateral aspect of upper arm across pectoral region

B Posteromedial aspect of lower limbs

C Vertical lines on pre or parasternal region of chest

D Posteromedial aspect of the spine

E Lines from mid third of clavicle to peri-areola region, may be bilateral.

F “V” shaped hyperpigmentation between temple and malar area over face

G “W” shaped hyperpigmentation over anterolateral area of face between temple and malar area

H Band of hyperpigmentation over lower part of face extending from angle of mouth to lateral aspect of chin

II. Melasma

Melasma or chloasma or mask of pregnancy has a prevalence ranging between 2.5% and 75% of pregnant women.16, 36 There are wide variation in the incidence of melasma of pregnancy from different studies. Raj et al 37 in a study reported incidence of 8.5%. Muzaffar et al further studied skin changes among 140 pregnant women in 1998 and reported incidence of 46.4%.38 The major differences in the incidence of melasma in the different studies were attributed to the fact that pigmentary changes are more discernible in fair-skinned individuals.16 Melasma consists of irregular, but well demarcated dark-brown macules on the face. There are three clinical patterns which are centrofacial, malar and mandibular. It tends to appear during the second trimester and more frequently in dark-haired, brown-eyed, dark-complexioned women.24 Sanchez et al39 related the pathogenesis of melasma to elevated oestrogen, progesterones, MSH levels, genetic predisposition and increased number of melanocyte, resulting in excessive deposition of melanin

21 in the epidermis, dermal macrophages, or both.40 In most cases gestational melasma will resolve postpartum.41 Treatment of severe postpartum melasma involve use of preparation containing hydroquinone, topical corticosteroids and tretinoin.41

B. HAIR CHANGES IN PREGNANCY

I. Hirsutism

Hirsutism is an excess of terminal hair growth in women in a pattern more typical of men.42 Androgen-dependent growth areas affected include the upper lip, cheeks, chin, central chest, breasts, lower abdomen, and groin.42 During pregnancy most women develop some degrees of hirsutism mostly pronounced on the face, 43 and less often on the arms, legs, and back.14 Besides, suprapubic midline hair growth with a male-pattern distribution may also be increased during pregnancy.44 Scalp hair becomes fuller during pregnancy, which correlates with an increase in the hair mean shaft diameter when compared with the non-pregnant state.45

Though the cause is unknown, it is suggested to have resulted from increased androgen and oestrogen.43 The excessive hair has also been reported by Lynfield to be due to prolonged anagen phase producing a thicker than normal growth during pregnancy.46 When severe hirsutism occurs, androgen-secreting tumours of the ovary, luteomas, lutein cysts, or polycystic ovary disease should be excluded.14

This excessive hair regresses within 6 months postpartum. Where treatment is indicated it consists of education, reassurance, and cosmetic treatment of unwanted hair postpartum. There are many permanent and non-permanent options for treating hirsutism. These include shaving, waxing, electrolysis, and laser epilation.45

II. Male-pattern baldness

Some women develop diffuse thinning or frontoparietal recession; such changes may not be fully reversible postpartum.47 The causes are unknown but inhibition of gonadotropic activity secondary to high-steriod levels may play an important role.27

C. NAIL CHANGES IN PREGNANCY

Nails grow at an accelerated rate during pregnancy. Barankin et al47 reported transverse grooves, leukonychia, subungual hyperkeratosis, distal onycholysis, softening and brittleness as the nail changes among the pregnant women they examined. Elling et al observed longitudinal melanonychia.44 Mahboobe et al,48 reported prevalence of nail fragility to be 12.8%. Most of these conditions resolve within 6 months to 1 year postpartum. The pathogenesis of these changes is unknown.43

D. GLANDULAR ACTIVITY IN PREGNANCY

I. Eccrine gland

Eccrine sweating activity progressively increases during pregnancy and may cause hyperhydrosis, miliaria and dyshydrotic eczema.43 In a study of 607 pregnant women, Kumari et al.16 reported miliaria in 1.65% of them. The cause is unknown, but it may be related to some physiological adaptations which include alterations in autonomic nervous system function producing increase vasomotor activity resulting in excess sweating. Weight gain and increased thyroid activity may also play a role.49-51 During pregnancy, raised thyroid activity and relative iodine deficiency cause the thyroid gland to hypertrophy and to increase its iodine uptake.49

There is no effective treatment for the increased eccrine sweating. In troublesome cases a

20% solution of aluminum chloride hexahydrate in ethyl alcohol applied every night for 1 week, and then as necessary, may be effective to control the excessive sweating.51

II. Apocrine gland

Apocrine activity decreases during pregnancy.43 The cause of this decreased activity is unknown40 however, hormonal influences probably play a causative role, and there is still debate as to the importance of estrogen, progesterone, and cortisol.51 Patients with hidradenitis suppurativa may show temporary improvement; however this condition may rebound postpartum.43

III. Sebaceous gland (Acne vulgaris)

Increased sebaceous gland activity occurs in pregnancy which results in acne vulgaris.

Maya et al40 has linked the enhanced sebaceous gland function to increased circulating levels of oestrogen. The sebaceous gland hyperactivity and hypertrophy has unpredictable effects on acne and promotes the formation of small brownish papules at the areola known as

Montgomery tubercles which tend to resolve postpartum.40 Acne vulgaris may develop for the first time during pregnancy; preexisting acne may be exacerbated; or it may occasionally improve completely.44 The unpredictable effect of pregnancy on acne was demonstrated by

Muzaffar et al38 in a study of 19 cases of pregnancy induced acne when they noted regression of acne in 11( 57.9%) cases and aggravation of the condition in 8 (42.1%)cases. An earlier study by Ratzer in 1964 reported improvement of acne to be 58% among 400 pregnant women.52 The improvement in acne was due to therapeutic and beneficial effects of eostrogen.

Treatment of acne vulgaris in pregnancy is not often optimized as a result of the lack of safety data and unified recommendations on the use of various anti-acne therapies.53 Topical

24 medications such as antibiotics, benzoyl peroxide, azelaic acid, and salicylic acid are recommended as first-line treatment. Second-line agents that can be used include macrolide, cephalosporin, penicillin, zinc compound, and/or light-based therapy.53 Both oral and topical retinoids, tetracyclines, and hormonal therapy are contraindicated in pregnancy.

E. CONNECTIVE TISSUE CHANGES

I. Striae gravidarum

Striae gravidarum is a common complaint among pregnant women.4 Muzaffar et al38 reported incidence of 90%. In another study of 607 pregnant women by Kumari et al16 the incidence was put at 79.7%. Raj et al37 reported incidence of 75% while Chang found the incidence of 55%.54 In another study by Yamaguchi et al,55 the prevalence of striae gravidarum was 39.1%. Striae gravidarum has a low prevalence in blacks and primigravidae.16, 55 Stretch marks are linear, pink to violaceous atrophic lines that develop opposite the skin tension lines.

They result when physical factors (stretching secondary to increase in the abdominal girth) and hormone (relaxin, oestrogen and corticosteroids) interact to cause thinning of elastin fibres and fibrillin microfibrils in the dermis. Familial tendency and race also tend to play a role in the development of striae in pregnancy as it is uncommon in Asian and African-American women.14 Most striae shrink postpartum, although they usually do not disappear completely.56

Treatment is non-specific. Postpartum treatments include topical tretinoin and laser treatment.57

F. VASCULATURE/HAEMATOLOGIC CHANGES

I. Spider angiomas

Spider angiomas markedly increase during pregnancy and it affects 10-15% of black women and 70% of whites.44,50,58,59 Bean et al60 reported prevalence of spider angiomas to be

67% among whites and 11.3% among blacks. Muzaffa et al reported very low incidence of 1.4% among 140 pregnant women studied in Lahore, Pakistan.38 This difference was credited in part to the dark complexion of the women, making the nevi less perceptible in blacks. They usually appear between the second and fifth month of pregnancy. They are macular or papular, red, telangiectatic puncta with radiating branches and surrounding erythema and are most commonly found in areas drained by the superior vena cava (the neck, throat, face, upper chest, arms, and hands).43 High oestrogen states is responsible for appearance of spider angioma.43 Alternative theory for formation of spider angioma is due to high level of angiogenesis because of the demand of vascular placental during pregnancy.61

Many spider angiomas regress within 7 weeks postpartum, therefore treatment should be avoided during pregnancy.51 About 10% will persist after postpartum period.51 These group of patients can be treated with low voltage electrodesiccation, cryosurgery or vascular lasers.51,62

II. Palmar erythema.

This condition occurs in 66% of white women and 33% of black women beginning in the first trimester.25,48,50 Muzaffa et al38 reported 12.1% of pregnant women to have palmar erythema in their study. Kumari et al16 studied 607 pregnant women and no case of palmar erythema was seen. This low incidence, like the low incidence of spider nevi, was related to less visibility in darker skin.45 The pathogenesis is due to high oestrogen state and/or angiogenesis factor, increased blood flow and a genetic predisposition.51

Palmar erythema fades soon after delivery, usually in 1–2 weeks postpartum, so no treatment is required.50, 51, 63

III. Varicosities

Varicosities are most common in the haemorrhoidal (anus), vulva and saphenous (leg) veins appearing in 40% of pregnant women during the 3rd month.49,60. Muzaffa et al in their study in Lahore Pakistan reported varicosities of lower leg only in 2.8% of cases.38 In another study by Raj et al37 varicose veins was seen only in six (0.5%) out of 1,175 pregnant women.

The differences in incidence in studies are due to customs, habits and posture the pregnant women adopt while in sitting position and working which vary among different races.38 Martin et al43 reported combination of factors responsible to include familial tendency, increased elastic tissue fragility in the blood vessels and increased venous pressure in the femoral and pelvic vessels due to compression from an enlarging uterus.41 Activities such as prolonged standing and sitting that contribute to obstruction of venous return may be exacerbating factors.38

Varicosities tend to regress after delivery, but not completely.38

When treatment is indicated, the goal of therapy is to collapse the distended superficial veins without impairing the circulation. Treatment of leg varicosities includes frequent elevation of the legs, sleeping in Trendelenburg position, lying in a left lateral decubitus position, light exercise, avoidance of prolonged sitting and standing, and avoidance of clothing that interferes with venous return.38,63,64 For persistent leg varicosities, postpartum venous stripping, endovascular ablation, endovascular sclerotherapy, or radiofrequency techniques may be beneficial. For symptomatic haemorrhoids, sitz baths, astringent compresses, laxatives, suppositories, and topical anaesthetics are very helpful.38,51

IV. Non – pitting oedema

This is present in about 50% of pregnant women during the third trimester.50 In a study by Muzaffa et al,38 he reported prevalence of 48.6%. Nkwo65 reported a prevalence of 8.5% among 1000 pregnant Igbo women in Nigeria. Oedema of the lower extremities not associated with preeclampsia or eclampsia develops in about 70% of pregnancies.51 This oedema is generally apparent in the morning, but improves with activity during the day. Oedema commonly involves the face and extremities and is thought to be secondary to sodium and water retention in conjunction with increased capillary permeability.40 Additional factor causing fluid retention in the extremities is attributable to increase hydrostatic pressure in the blood vessels due to reduced blood return.66 Patients should also be screened for other causes of oedema such as cardiac, renal, pre-eclampsia and eclampsia. Resolution of the oedema invariably occurs postpartum. Treatment where needed includes elevation of lower extremities, sleeping in a Trendelenburg position, and wearing loose clothing, exercise and reduction of salt intake.38

G. MUCOUS MEMBRANE CHANGES IN PREGNANCY

I. Pregnancy gingivitis

During pregnancy the gingivae enlarge, darken and become red and swollen in up to 80% of pregnant women.67 Muzaffa et al38 reported prevalence of 16.4% among 140 pregnant women studied. In another study of 607 pregnant women by Kumari et al16 he reported prevalence of

1.5%. The difference in prevalence is partly due to rarity of vitamin-C deficiency in the study population by Kumari.38, 43 The cause is unknown, however the pathogenesis of the hyperaemia and oedema in pregnancy gingivitis is linked to high progesterone, local irritation and nutritional deficiency.43, 67

2. SOME DERMATOSES AFFECTED BY PREGNANCY

A. INFLAMATORY DISORDERS

1. Atopic Dermatitis (AD)

Atopic dermatitis could occur for the first time during pregnancy in a person with atopic diasthesis.19 Atopic dermatitis is considered to be quite common during pregnancy.67 It is a multifactorial disease influenced by genetic predisposition and environmental factors. This inflammatory condition is dependent on the production of cytokines by allergen-specific T- helper 2 (Th2) Cells.68 Pregnancy is suggested to be aTh2 condition.69 Thus AD would be expected to flare during pregnancy. In a prospective study by Vaughan et al70 he reported prevalence of AD to be 36% (72 of 200) of pregnant women presenting to a specialty clinic for pregnancy dermatoses. The condition is likely to worsen than remit during pregnancy.71-72 The exacerbation is partly attributable to the pruritus of pregnancy.72

Atopic dermatitis flare in pregnancy is not known to cause adverse fetal outcome, however breast-feeding difficulties due to nipple eczematization and post-partum irritant hand dermatitis could be a problem.73

Treatment of atopic dermatitis in pregnancy should emphasize the use of emollients since they can be used safely during pregnancy. Topical steroids are relatively safe except for the very potent ones.74 When atopic dermatitis remains after optimizing topical steroids, narrow-band

UVB can be used as the safest second-line treatment option in pregnancy.74

II. Psoriasis

Chronic plaque psoriasis is the most common type of psoriasis to develop or worsen in pregnancy.75 The course of psoriasis in pregnancy is unpredictable, however, it is more likely to improve than worsen in up to 40% to 63% of pregnant women.76,77 The number of

29 patients whose psoriasis improve during pregnancy is approximately double the number of patients whose psoriasis worsen during pregnancy.78, 79 This is attributed to the high levels of interleukin-10 in pregnancy which has favourable effect on the course of the disease.14

B. INFECTIONS

The increased incidence of certain skin infections in pregnancy has been attributed to the immunosuppressive effects of high serum levels of oestrogen.80 This subsequently lead to decreased cell mediated immunity, impaired neutrophil functions, decreased activity of natural killer cells and impairment of local antibody responses.80 The following infectious dermatoses are affected by pregnancy:

I. Candidiasis

Candidiasis is usually caused by the yeast–like fungus called Candida albicans. Frerich et al81 reported that 56% of women have episodes of candidiasis at some time during pregnancy.

Candidal vaginitis can be seen in up to 56% of pregnant women. Akerele et al82 studied 578 pregnant women in Imo state, Nigeria and found out that 118 (20.4%) of them had vaginal candidiasis. Parish LC et al83 observed symptomatic vulvovaginal candidiasis in 10% of pregnant women in first trimester and 23% in the third trimester.

Nystatin is minimally absorbed and is effective for treatment of vaginal candidiasis. Vaginal use of imidazole such as fluconazole is probably safe during later stages of pregnancy especially at lower doses of 150mg per day.84

II. Pityriasis versicolor

Data on the prevalence of pityriasis versicolor (PV) in pregnant women are few in literature. Zampino et al85 reported frequency of PV during pregnancy to be 5.7%. The lesions

30 are multiple macules of various sizes and shapes coalescing together to produce fine scales. It is caused by a yeast infection Pityrosporum orbiculare.

III. Dermatophytes infections

Dermatophytes are fungi that require keratin for growth as their nutrient source and can cause infection of the skin, hair and nails.86 The three genera known today are Epidermophyton,

Microsporum and Trichophyton.87 The most common and most widely distributed is

Trichophyton rubrum.88 Lohoue JP et al reported athletes foot in 22% of 430 pregnant women studied and 71.84% of the dermatophytes were due to Trichophyton rubrum.89 Topical azoles are safe and effective for the treatment of superficial fungal infections. There is risk of teratogenicity associated with systemic azoles and is not recommended in pregnancy.90

IV. Herpes zoster

Herpes zoster is caused by reactivation of latent varicella-zoster virus (VZV) at dorsal root ganglia. It presents with vesicular rashes, pain and itching along the distribution of a dermatome.91 Herpes zoster usually poses no risk to the pregnant woman and there is no need for antiviral therapy.92

V. Herpes simplex virus infection

Herpes simplex virus (HSV) infection is one of the most common sexually transmitted diseases worldwide.93 Herpes simplex virus type 1 and type 2 commonly cause orofacial and genital herpes respectively. In U.S.A, approximately 22% of pregnant women are infected with HSV-2.93

HSV infection presents with blistering and ulceration of external genitalia, vulva pain, dysuria and vaginal discharges. Treatment is necessary for severe diseases with antiviral such as

31 acyclovir and valacyclovir, the drugs of choice to prevent fetal infection which can lead to intrauterine death, and severe malformation and premature birth.94

VI. Genital warts in pregnancy

Genital warts (condylomata acuminata) are caused by human papilloma virus (HPV) type

6 and 11. They are moist, cauliflower-like masses of variable sizes and are usually sexually transmitted.95 It is estimated that 1 to 3% of pregnant women are infected.96 Genital warts can proliferate during pregnancy due to down-regulation of the cell-mediated immune response and increased blood supply to the genital area.95 There is risk of recurrent respiratory papillomatosis and vertical transmission of human papilloma virus (HPV) from women with genital warts to their progeny.

There are no adequate data to indicate whether treatment of external genital warts eliminates infectivity; thus primary goal of treatment that are safe during pregnancy such as trichloroacetic acid, cryotherapy, surgical excision, laser therapy and electrosurgery, is to ameliorate symptoms and remove symptomatic warts.97

C. CUTANEOUS TUMOURS

I. Pyogenic granuloma of pregnancy

Pyogenic granuloma of pregnancy appears as a deep red or cherry–red, oval, friable, soft, pedunculated or sessile lobule. The prevalence has been reported to be between 2-27% among pregnant women during their 2nd and 5th months of pregnancy.49,51,98 Usually, it occurs with extensive gingivitis.49 The cause of the condition is unknown, however, it has been related to hormonal influences on the tissue response to trauma or irritation such as caries.51 Treatment is not necessary as the lesion typically regress postpartum. However, prompt consultation and

32 possible excision may be indicated if lesion is big, very painful, interferes with eating, bleeding or cosmetically disfiguring.43, 49, 51

II. Molluscum fibrosum gravidarum

This is also known as skin tag or acrochordon. Rathore et al17 reported prevalence of skin tag to be 3.3%. These are small, soft, pedunculated lesions. Pregnancy, obesity, diabetes mellitus and typical atherogenic lipid profile seen in insulin resistant states are often associated with development of skin tags.99

It may form on the face, neck, axillae, chest, groin or infra-mammary region particularly during second and third trimester.4 It may regress following child birth.4 The pathogenesis has been linked to hyperoestrogenic state in pregnancy.4

Treatment is not necessary, but skin tags can be removed with grade 1 scissors, cryotherapy, or electrodessication.99

D. MISCELLANEOUS

I. Pruritus

Many pregnant women complain of pruritus. The prevalence of pruritus vary widely in different studies. Pruritus in pregnancy from all causes was seen in 17% by Winton et al.49 Wong et al51 reported that 20% of pregnant patients are affected by pruritus with no associated pathology. Roger et al100 reported prevalence of 18%, Kenyon A.P.101 31%, Shivakumar et al102 was 58.8%, while Raj et al37 documented 73.6%. Pruritus may be part of a physiological phenomenon or a pregnancy–related dematoses such as intrahepatic cholestasis of pregnancy.

II. Acanthosis nigricans (AN)

Acanthosis nigricans is a symmetrical eruption characterized by hyperpigmented velvety skin lesions in any location but usually in the axillae, groin, neck, infra-mammary area, antecubital, popliteal and umbilical areas.103 It is known to occur in gestational diabetes, glucose intolerance or obesity. However, Kroumponzos et al104 has reported a 35 year old pregnant woman with acanthosis nigricans without history of gestational diabetes or glucose intolerance.

3. PREGNANCY-SPECIFIC DERMATOSES (PSDs).

I. Atopic eruption of pregnancy (AEP)

Atopic eruption of pregnancy is also known as pruritic folliculitis of pregnancy, papular dermatitis of pregnancy, eczema of pregnancy or prurigo of pregnancy.105,106 It is a benign pruritic disorder of pregnancy. AEP has a prevalence of 50% making it the most common pregnancy specific dermatosis.23

The main clinical features of AEP are pruritus, prurigo lesions and eczematous–looking lesions located in the typical atopic sites. The aetiology of AEP is still not fully clarified but is always linked with a personal and/or family history of atopy.107 The pathogenesis is thought to be triggered by predominantly T helper –2 immune response.

Patient should be informed that the disease is related to pregnancy and is a benign, self-limited disorder.108 In mild cases, mild to moderate topical steroid creams may be used while potent topical steroid creams or oral steroids are used in severe cases. Oral antihistamines such as cetirizine, loratadine and emollient cream with urea can be used to reduce pruritus.109

II. Polymorphic eruption of pregnancy (PEP)

PEP synonyms include pruritic urticarial papules and plaques of pregnancy (PUPPP), toxic erythema of pregnancy, toxaemic rash of pregnancy and late-onset prurigo of

34 pregnancy.105 It is a benign self–limited pruritic, papulo-urticarial inflammatory disorder that usually affects primigravidae in the last trimester.106 The incidence of PEP is about 1:160 pregnancies.105

PEP begins in the striae gravidarum, appears suddenly, itches strongly, and can become erythematous with urticarial papules and plaques; the peri-umbilical region is spared. The pathogenesis of PEP is not known . Rudolph et al110 linked the condition with existence of multiple gestation pregnancy and excessive maternal weight gain.

In mild cases, when limited area of skin is affected, mild to moderate topical steroid creams may be effective. In severe cases, potent topical steroid creams or oral steroids (rarely required) may be used.105 Oral antihistamine and emollients creams can be given to reduce pruritus.

III. Pemphigoid gestationis (PG)

This was previously called herpes gestationis.56 It is a rare autoimmune vesiculobullous disorder that is intensely pruritic and develops in late pregnancy.109 PG has a world-wide distribution with an approximate incidence of 1 in 60,000 pregnancies.109 Typically, urticarial erythema, papules and plaques as well as tense blisters appear on the abdomen and the periumbilical region.16

The pathogenetic basis of PG asserts that circulating complement–fixing immuno globulin (Ig) G antibodies of the subclass IgG1 bind to a 180kDa protein (BP-180) within the hemidesmosomes of the basement membrane zone (BMZ) and this later lead to tissue damage and blister formation.111 PG lesions usually resolve after delivery. In severe cases, oral steroids

(prednisolone) 0.5-1mg/kg/day, may be required to rapidly get the diseases under control.105 In

35 more severe cases, plasmaphoresis can be considered; after delivery other immunosuppressive drugs can be considered. Oral antihistamine and emollient can be used to relieve pruritus.105

IV. Intrahepatic cholestasis of pregnancy (ICP)

Intrahepatic cholestasis of pregnancy (ICP) is also called pruritus gravidarum or prurigo gravidarum.56 It was first described by Kehrer in 1907 as recurrent jaundice of pregnancy.112 ICP occurs in one out of 146 to 1,293 pregnancies in the United States.14 Neerja et al113 reported prevalence of 1% in their study while Sharath et al,114 found prevalence of 4%. A family history of the condition is common, and there is association with the presence of human leukocyte antigen-A31(HLA-A31 and HLA-B8).14 It presents in late pregnancy with massive, severe generalized pruritus, which may be associated with clinical jaundice without any skin lesion.115

Intrahepatic cholestasis of pregnancy is due to defect in the excretion of bile salts with resultant elevation in serum bile acids of greater than 11.0 µMol/L for a positive diagnosis.116 Aspartate and alanine transaminases levels and other liver function tests may be mildly abnormal.56 It is a disorder with severely increased fetal risks if not handled with care. Fetal risk include intra- partum fetal distress, stillbirth and premature births.99

Patient with mild pruritus may be treated with oral antihistamines. More severe cases require ursodeoxycholic acid to relieve pruritus and improve cholestasis while reducing adverse fetal outcomes.99 Current evidence does not support treatment with S-adenosylmethionine, cholestyramine, Phenobarbital or corticosteroid because they do not improve fetal prognosis.54

CHAPTER THREE

AIMS AND OBJECTIVES OF THE STUDY

GENERAL OBJECTIVE

1. To determine the pattern of cutaneous changes among primigravidae attending the antenatal clinic (ANC) of OAUTHC, Ile-Ife.

SPECIFIC OBJECTIVES

1. To determine the prevalence of skin changes among primigravidae at the antenatal clinic

of OAUTHC.

2. To document the clinical pattern of the skin changes in these pregnant patients.

3. To correlate the documented skin changes with the gestational age (trimester) of

pregnancy.

CHAPTER FOUR

JUSTIFICATION OF STUDY

The skin is a known cutaneous marker to physiological and pathological events taking place in an individual. Established correlations by research could contribute to early diagnosis of underlying systemic problems in these pregnant women.

There is a need for baseline data of skin changes in pregnant women to serve as a template for further research in this environment and this study may also help to predict the occurrence of skin diseases as pregnancy advances.

In addition, it is hoped that the study will assist in distinguishing between common skin changes in pregnancy and those that are of more serious implication for the pregnant patient or her unborn child.

Maternal morbidity and mortality is an index for measuring the level of development in any society; therefore any research that will lead to improvement in maternal health is of great importance.

CHAPTER FIVE

SUBJECTS, MATERIALS AND METHODS

Study Location.

This study was conducted at the Department of Obstetrics and Gynaecology of the

Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Osun State. It is located in the South–West geopolitical zone of Nigeria.

OAUTHC is a 650 bedded tertiary health care institution, a referral centre for private hospitals, comprehensive health centres and secondary hospitals from neighbouring states such as Ondo, Ekiti, Oyo and parts of Kwara and Edo states.

Sample Size

The sample size was calculated based on documented prevalence of 87.9%17 in a similar study carried out in a tertiary hospital in India as there is paucity of data in this environment with no documented prevalence.

Sample size for descriptive cross-sectional study when studying proportion with population <10,000 will be:117 nf = n 1+ n/N nf = The desired sample size when population is less than 10,000.

N = The estimate of the population size. n = The desired sample size when the population is more than 10,000.117

n = Z2Pq d2 P = The proportion in the target population estimated to have a particular

characteristic = 87.9% (in this case 0.88)

Z = The standard normal deviation (using 95% confidence level = 1.96) d = Degree of accuracy desired (precision) set at 0.05 q = 1.0-P =0.12

So, n = (1.96)2 x 0.88x 0.12 (0.05)2

= 0.4057/0.0025

= 162.3

Estimated annual primigravidae patients presenting at antenatal clinic (ANC) of Department of

Obstetrics and Gynaecology OAUTHC, Ile-Ife is 2500 nf = 162.3 1+162.3/2500

= 162.3/1.0649

= 152.41

The minimum sample size of 152.4 was calculated and this was rounded up to 160. It was further increased (by half) to 240 in other to pick possible rare cutaneous changes like pemphigoid gestationis, and intrahepatic cholestasis of pregnancy e.t.c., to correct for attrition and also for multivariate analysis.

STUDY DESIGN

This study is a descriptive cross-sectional observational study.

STUDY POPULATION

Subjects

A total of 480 subjects, comprising of 240 consecutive primigravidae attending ANC at

OAUTHC, Ile-Ife and 240 suitably matched control of the same age that have never been pregnant were recruited into the study from primary infertility clinic, general population and examined at the Dermatology clinic of OAUTHC, Ile-Ife.

Data Collection Method

Data was collected from a total of two hundred and forty primigravidae using author administered proforma. Ninety-seven and 143 subjects were recruited into the study in first and second trimesters respectively. The 143 subjects recruited in second trimester had the history of their first trimester skin changes taken and added to the 97 subjects to make a total of 240 subjects. Patients were examined thoroughly in a well-lit room, the skin findings and the self- reported skin changes were documented against the trimester of pregnancy at which they appeared. Patients were then subsequently followed up during their second and third trimesters of pregnancy for persistence of documented skin changes or onset of new skin changes.

Informed written consent of the patient for the study was obtained before the interview and clinical examination. Photographs of the skin lesions were also taken using digital camera.

SELECTION CRITERIA

Inclusion Criteria for the patient

1. Patient pregnant for the first time ever (primigravidae).

2. A negroid African primigravidae.

3. Individual who gave informed consent.

4. Individual who was 18 years and above.

Exclusion Criteria for the patient

1. Patients on drugs that cause hyperpigmentation and striae.

2. Patient with systemic disease such as diabetes mellitus.

3. Patients with chronic disease such as chronic renal failure, chronic liver disease.

4. HIV seropositive individuals.

Inclusion criteria for control

1. Individual who was 18 years and above.

2. Individual that had never been pregnant.

3. Individual who gave informed consent.

4. Individual without any chronic disease such as diabetes mellitus, HIV, chronic renal failure,

chronic liver disease.

Exclusion Criteria for the control

1. Patients on medications that cause hyperpigmentation or striae.

2. Individual that did not give informed consent.

3. Individual with systemic diseases such diabetes mellitus, and HIV.

4. Individual with chronic diseases such as chronic renal disease.

Lower age limit of 18 years was chosen because individuals below this age are not adult and by implication could not give informed consent.

ETHICAL ISSUES

Approval of Ethics and Research Committee of the hospital was sought and obtained before the study.

CLINICAL EVALUATION

The purpose of the study and its advantages were explained thoroughly to all participants in the language they understood. Thereafter, informed written consent was obtained from all the participants recruited into the study.

PROTOCOL 1: CLINICAL DIAGNOSIS.

The patients were diagnosed to be pregnant for the first time (primigravidae) and confirmed using pregnancy test (PT) or obstetrics ultrasound scanning (USS). Attention was also paid to number of fetus using USS.

PROTOCOL II: CLINICAL HISTORY

Data was collected from the patients by the investigator using proforma that included socio-demographic data such as age, occupation and educational qualification. Gestational age of pregnancy, presence and duration of the skin changes or lesions in pregnancy were noted.

Other relevant history to suggest possible complication to the mother or fetus was sought for.

To avoid inter observer errors interviews, clinical examination and photographs of the lesions were conducted by the investigator alone.

PROTOCOL III: CLINICAL EXAMINATION

Thorough physical examination was conducted in a well-lit room, during which the whole skin, nail and hair were examined for any abnormality. Pictures of the skin changes were taken with a digital camera.

Weight of each patient was obtained using weighing scale and height obtained using standiometer. Magnifying lens was used where appropriate to make small, tiny, vascular

43 changes, small scales and skin markings more obvious. Skin lesions were treated appropriately without interfering with pregnancy state.

PROTOCOL IV: LABORATORY INVESTIGATION

The patients underwent the following investigations, pregnancy test (PT) or obstetric

USS to confirm pregnancy, urinalysis, HIV screening test to exclude HIV infection. Also where indicated, fasting or random blood sugars were done to exclude diabetes mellitus. There was no indication for liver function test, renal function test, bacteriological studies and skin biopsy.

STATISTICAL ANALYSIS

Data was analyzed using Statistical Package for the Social Sciences (SPSS) version 16.0.

Data was represented using descriptive statistics such as tables, charts as necessary and inferential statistic such as Chi square and Friedman’s tests were done.

LIMITATIONS OF THE STUDY

1. Never pregnant controls and first ever pregnant subjects (primigravidae) were self-reported

and might deny previous pregnancies or pregnant without been aware of it.

2. Community based study such as from private hospitals, traditional birth attendants, mission

houses, primary health care facilities may be more appropriate to pick some pregnancy

specific dermatoses.

3. Pregnant patients who were seronegative for HIV might still be in the window period and

therefore might be difficult to be excluded using the rapid test kits.

4. Some patients or controls might deny the history of use of medications known to cause skin

changes (e.g. melasma) similar to that seen in pregnancy since they are self-reported.

CHAPTER SIX

RESULTS

6.1 SOCIO-DEMOGRAPHIC CHARACTERISTICS OF THE SUBJECTS AND

CONTROLS

The study involved 480 participants comprised of 240 primigravidae recruited consecutively from antenatal clinic (97 subjects in first trimester and 143 subjects in second trimester as in figure 2) and 240 never pregnant control subjects from the primary infertility clinic and general population between February, 2013 and January, 2014.

Table 1 shows the socio-demographic characteristics of the subjects and controls.

The age range for both the subjects and controls were from 18 years to 40 years (median

27.0 years). The mean ages for subjects and controls were 27.53±3.88 years and 27.15±4.17 years respectively.

One hundred and seventeen (48.8%) each for subjects and controls were in the age range 26-30 years, this was followed by the subjects and controls within the 21-25 years age range that is,

45 sixty three (26.2%) for each. Nine (3.8%) subjects and controls were each less than 20 years of age. The remaining 51 (21.3%) each for subjects and controls were 30 years and above.

More than half of the patients i.e. 207 (86.2%) subjects and 216 (90.0%) controls had tertiary education. Twenty six (10.8%) subjects and 19 (7.9%) controls stopped at secondary school, this was followed by 5 (2.1%) subjects and 4 (1.7%) controls with primary education.

Two (0.8%) subjects and one (0.4%) of the controls had no formal education.

Majority of the subjects were traders 60 25.0) and civil servants 64 26.6). Forty six

19.2%) of the subjects were students. A large proportion, that is 122 50.8) of controls were students. The professionals constituted 24 10) of the subjects and 23 9.6) of the controls.

There was no statistically significant relationship between socio-demographic characteristic of the subjects and skin changes in pregnancy.

Table 1: Socio-demographic characteristic of the Subjects and Controls

Pregnant cases Control n=240 n=240 Significant Characteristics Frequency Percentage Frequency Percentage level N % N %

Age (years) <20 9 3.8 9 3.8 p= 0.52 21-25 63 26.2 63 26.2 26-30 117 48.8 117 48.8 df= 4 31-35 47 19.6 47 19.6 36-40 4 1.7 4 1.7 2 = 3.21 Total 240 100.0 240 100.0

Occupation Unemployed 33 13.8 12 5.0 p= 0.11 Student 46 19.2 122 50.8 Trading 60 25.0 22 9.2 df= 4 Civil servant 64 26.6 52 21.6 Professional 24 10.0 23 9.6 2 =7.53 Others 13 5.4 9 3.8 Total 240 100.0 240 100.0

Education level No education 2 0.8 1 0.4 p= 0.63 Primary 5 2.1 4 1.7 Secondary 26 10.8 19 7.9 df= 3 Tertiary 207 86.2 216 90.0 Total 240 100.0 240 100.0 2 =0.89

Mean age years) 27.53±3.88 27.15±4.17

Median age 27.00 27.50 years)

Others= Farmers, clergy.

6.2a. GENERAL PREVALENCE OF PREGNANCY ASSOCIATED SKIN CHANGES.

Figure 1 shows the general prevalence of pregnancy associated skin changes among the subjects and the controls. Two hundred and twelve (88.3%) had skin changes in first trimester, while 28 (11.7%) subjects had no skin changes. More and equal number of subjects i.e. 236

(98.3%) had skin changes each in second and third trimesters, while 4 (1.7%) subjects each had no skin changes during these trimesters. Only 114 (47.5%) of the controls had skin changes while 126 52.5) had no skin changes.

Figure 1: General prevalence of pregnancy associated skin changes among subjects and controls

98.3 98.3 100 88.3 90

 60 52.5 47.5 50 Present Absent

Frequency 40

20 11.7

10 1.7 1.7 0 1st trimester 2nd trimester 3rd trimester Control General prevalence of skin changes

6.2b. GENERAL PREVALENCE OF PREGNANCY ASSOCIATED SKIN CHANGES.

Table 2 shows general prevalence of pregnancy associated skin changes among subjects.

Twenty eight (11.7%) in first trimester, 4 (1.7%) each in second and third trimester had no skin changes in pregnancy. The prevalence of the subjects with only one skin change were 17 (7.0%) in first trimester, 5 (2.0%) in second trimester and 9 (3.8%) in third trimester. Subjects with more than one skin changes in pregnancy were the most common with prevalence of 195 (81.3%) in first trimester, 231 (96.3%) in second trimester and 227 (94.5%) in the third trimester.

Table 2: General prevalence of pregnancy associated skin changes among subjects

Number of skin Pregnant cases changes n=240

First trimester Second trimester Third trimester N (%) N (%) N (%)

None 28 (11.7) 4 (1.7) 4 (%)

One 17 (7.0) 5 (2.0) 9 (3.8)

More than one 195 (81.3) 231 (96.3) 227 (94.5)

Total 240 (100.0) 240 (100.0) 240 (100.0)

6.3. TRIMESTER DISTRIBUTION OF SUBJECTS ENROLLED INTO THE STUDY.

Figure 2 shows the trimester distribution of subjects recruited into the study from the antenatal clinic.

Ninety-seven (40.4%) subjects in the first trimester and one hundred and forty-three (59.6%) subjects in the second trimester were recruited into the study from the antenatal clinic.

Figure 2: shows the trimester distribution of subjects recruited into the study from the antenatal clinic.

Subjects enrolled

59.6

50 40.4

40 %

Frequency 20

0 1st trimester 2nd trimester Subjects enrolled per trimester

6.4 PREVALENCE OF THE THREE CLASSES OF PREGNANCY ASSOCIATED

SKIN CHANGES.

Table 3 shows the prevalence of the three classes of pregnancy associated skin changes.

Physiological skin changes were the most common skin changes seen in all the three trimesters and were noticed in 185 (77.1%) subjects in first trimester, 228 (95.0%) subjects in second trimester, 227 (94.6%) subjects in the third trimester and only in 107 (44.6%) among the controls. Some dermatoses affected by pregnancy were the second commonest skin changes, and were seen in 80 (33.3%) subjects, 88 (36.7%) subjects, 121 (50.4%) subjects in first, second and third trimesters respectively and only in 19 (7.9%) of control. No pregnancy specific dermatoses were documented in this study in any category.

Table 3: Prevalence of the three classes of pregnancy associated skin changes in subjects and controls.

Skin changes Pregnant cases Controls n=240 N (%)

First Second Third Trimester Trimester Trimester N (%) N (%) N (%)

Physiological skin 185 (77.1) 228 (95.0) 227 (94.6) 107 (44.6) changes

Some other dermatoses 80 (33.3) 88 (36.7) 121 (50.4) 19 (7.9)

Pregnancy specific 0 0 0 0 dermatoses

N=Frequency

Majority of the pregnant women have more than one skin changes in pregnancy (Table 2).

6.5 PREVALENCE OF THE SUBCLASSES OF PREGNANCY ASSOCIATED SKIN

CHANGES.

Table 4 shows the prevalence of the subclasses of pregnancy associated skin changes in subjects and controls. Pigmentary skin changes ranked highest in first, second and third trimesters and were seen in 186 (77.1%), 230 (95.0%) and 229 (94.6%) pregnant categories respectively and only in 41 (17.1%) of controls. Glandular changes was the second highest skin changes in all the trimesters and was present in 99 (41.3%) in the first trimester, 139 (57.9%) in second trimester, and 128 (53.3%) in the third trimester while it was seen in 65 (27.1%) of the controls.

Nail changes were reported in 56 (23.3%), 113 (47.1%) and 103 (45.5%) patients in first, second and third trimesters respectively and only in 10 (4.2%) in the control population. Fifty five (21.7%) subjects had skin infection in first trimester, 80 (33.3%) in the second trimester, and

74 (30.4%) in third trimester while only 13 (5.4%) of control had skin infection. Connective tissue changes were noticed in 39 (16.2%) subjects in the first trimester, 90 (37.5%) subjects in second trimester and 94 (39.2%) subjects in the third trimester while 20 (8.3%) had it in control population. Twenty two (9.2%) subjects in the first trimester, 33 (13.8%) subjects in the second trimester and 32 (13.3%) in the third trimester had cutaneous tumour during pregnancy and 4

(1.7%) noticed it in controls. Hair changes were noticed in 16 (6.7%) subjects in first trimester,

45 (18.8%) and 46 (19.2%) in second and third trimesters respectively and 9 (3.2%) of controls.

Other dermatoses were seen in 15 (6.2%) subjects in first trimester, 83 (36.7%) subjects in

52 second trimester, 116 (50.4%) subjects in third trimester and 1 (0.4%) in controls. Vasculature changes were seen in first, second and third trimesters in 12 (5.0%), 72 (30.0%) and 99 (41.2%) subjects respectively and 2 (0.8%) in controls.

Mucus membrane changes were seen in 3 (0.8%) subjects in first trimester, 5 (1.7%) subjects in second trimester, and 4 (1.2%) subjects in the third trimester and 1 (0.4%) in controls.

Inflammatory diseases were noticed in 1 (0.4%) subject in first trimester, and 2 (0.8%) each in second and third trimesters and 4 (1.7%) in controls. Pregnancy specific dermatoses were not seen in any of the pregnant subjects examined.

Table 4: Prevalence of the subclasses of pregnancy associated skin changes in subjects and controls

Skin changes Pregnant cases Controls n=240 N (%) First Second Third Trimester Trimester Trimester N (%) N (%) N (%) Pigmentary 186 (77.5) 230 (95.8) 229 (95.4) 41(17.1)

Glandular 99 (41.3) 139 (57.9) 128 (53.3) 65(27.1)

Nail 56 (23.3) 113 (47.1) 103 (45.4) 10(4.2)

Infection 55 (21.7) 80 (33.3) 74 (30.8) 13(5.4)

Connective tissue 39 (16.2) 90 (37.5) 94 (39.2) 20(8.3)

Cutaneous tumor 22 (9.2) 33 (13.8) 33 (13.8) 4(1.7)

Hair 16 (6.7) 45 (18.8) 46 (19.2) 9(3.2)

Other dermatosis 15 (6.2) 83 (36.7) 116 (50.4) 1(0.4)

Vasculature 12 (5.0) 72 (30.0) 99 (41.2) 2(0.8)

Mucus membrane 3 (1.3) 5 (2.1) 4 (1.7) 1(0.4)

Inflammatory disease 1 (0.4) 2 (0.8) 2 (0.8) 4(1.7)

Pregnancy specific 0.0 0.0 0.0 0.0 dermatoses Majority of the pregnant women have more than one skin changes in pregnancy (Table 2).

6.6 PREVALENCE AND PATTERN OF PHYSIOLOGICAL SKIN CHANGES

Table 5a shows prevalence and pattern of physiological (pigmentary) skin changes in pregnant subjects and controls.

Nipple hyperpigmentation was the most common pigmentary changes in pregnancy among the subjects examined and was seen in 158 (65.8%) in first trimester and 197 (82.1%) each in second trimester and third trimester and 6 (2.5%) of controls. The second commonest pigmentary changes was areola hyperpigmentation and was seen in 147 (61.2%) subjects in first trimester, 184 (76.7%) in second trimester and 185 (77.1%) in third trimester and only in 5

(2.1%) of controls. Linea nigra was observed in 61 (25.4%) subjects in the first trimester, 180

(75.0%) subjects in the second trimester and 185 (77.1%) subjects in the third trimester. This is comparable to 19 (7.9%) seen in control population. Seventy five (31.2%) subjects had generalized hyperpigmentation in the first trimester, 112 (46.7%) subjects had it in second trimester and 115 (47.9%) subjects in the third trimester.

The other pigmentary changes in pregnancy in descending order of frequency seen during each trimester were; first trimester, hyperpigmentation of sun exposed area face and neck) 57

(23.8%), abdomen 49 (20.4%), breast 26 (10.8%), inner thigh 24 (10.0%), axillae 14 (5.8%), melasma 12 (5.0%), melanocytic naevi 2 (0.8%), Voigt’s line 2 (0.8%); second trimester, hyperpigmentation of sun exposed area face and neck) 81 (33.8%), abdomen 71 (29.6%), breast

35 (14.6%), inner thigh 33 (13.8%), axillae 23 (9.6%), melasma 22 (9.2%), melanocytic naevi 6

(2.6%), scar 3 (1.2%), Voigt’s line 6 (2.5%); third trimester, hyperpigmentation of sun exposed area face and neck) 79 (32.9%), abdomen 69 (28.8%), breast 37 (15.4%), inner thigh 31

(12.9%), axillae 23 (9.6%), melasma 21 (8.8%), Voigt’s line 11 (4.6%), melanocytic naevi 5

(2.1%), scar 4 (1.7%).

Table 5a: Prevalence and pattern of pigmentary (physiological) skin changes in pregnant subjects and controls.

Pigmentary skin Pregnant cases Controls changes n=240 N (%)

First Second Third Trimester Trimester Trimester N (%) N (%) N (%)

Nipple 158 (65.8) 197 (82.1) 197 (82.1) 6 (2.5) hyperpigmentation Areola 147 (61.2) 184 (76.7) 185 (77.1) 5 (2.1) hyperpigmentation Generalized 75 (31.2) 112 (46.7) 115 (47.9) 0 hyperpimentation Linea nigra 61 (25.4) 180 (75.0) 185 (77.1) 19 (7.9)

Sun exposed area 57 (23.8) 81 (33.8) 79 (32.9) 5 (2.1) Face and neck) Abdomen 49 (20.4) 71 (29.6) 69 (28.8) 1 (0.4)

Breast 26 (10.8) 35 (14.6) 37 (15.4) 1 (0.4)

Inner thigh 24 (10.0) 33 (13.8) 33 (13.8) 5 (2.1)

Axillae 14 (5.8) 23 (9.6) 23 (9.6) 4 (1.7)

Melasma 12 (5.0) 22 (9.2) 21 (8.8) 3 (1.2)

Melanocytic naevi 2 (0.8) 6 (2.5) 5 (2.1) 0.0

Scar pigmentation 2 (0.8) 3 (1.2) 4 (1.7) 3 (1.2)

Voigt’s line 1 (0.4) 5 (2.1) 10 (4.2) 0.0 (Type B) Voigt’s line 1 (0.4) 1 (0.4) 1 (0.4) 0.0 (Type B coexisting with type A)

Majority of the pregnant women have more than one skin changes in pregnancy (Table 2).

Table 5b shows prevalence and pattern of other physiological skin changes in pregnancy and controls.

The hair change noticed in this study was hirsutism which was seen in 13 (5.4%) subjects in the first trimester, 33 (13.8%) subjects in the second trimester and 34 (14.2%) subjects in the third trimester and only 8 (3.3%) had hirsutism in the control group. No case of male-pattern baldness was seen in any of the trimesters during the study.

Increased growth was the most common nail change in pregnancy in all the trimesters and was self-reported in 43 (17.9%) subjects in first trimester, 94 (39.2%) subjects in second trimester and 89 (37.1%) subjects in third trimester and only in 4 (1.7) in controls. The second most common nail change is leuconychia and was observed in 18 (7.3%), 29 (12.1%) and 26

(10.8%) subjects in first, second and third trimesters respectively comparable to 3 (1.2%) in controls. Nail fragility was reported in 3 (1.2%) subjects in first trimester, 13 (5.4%) subjects in second trimester, and 12 (6.0%) in the third trimester and 2 (0.8%) in controls. The other nail change in pregnancy was melanonychia seen in 1 (0.4%) subject during the first trimester, 3

(1.2%) subjects each in second and third trimesters and only seen in 1 (0.4%) of the controls.

Among the glandular changes hyperhidrosis was reported in 16 (6.7%) subjects in first trimester, 55 (22.9%) subjects in the second trimester, 59 (24.6%) subjects in the third trimester

56 and only in 3 (1.3%) of controls. Heat rashes were seen in 6 (2.5%), 11 (4.6%), 8 (3.3%) subjects in first, second and third trimesters respectively while it was seen in 11 (4.6%) of controls. Acne vulgaris was seen in 84 (35.0%) subjects during the first trimester, 100 (41.7%) subjects in second trimester, 85 (35.4%) subjects in third trimester and 58 (24.2%) seen in the control group.

Connective tissue (striae) changes was seen in 39 (16.3%) subjects in first trimester, 90

(37.5%) subjects in second trimester, and 88 (36.7%) subjects in the third trimester comparable to 18 (7.5%) seen in control population.

Non-pitting oedema of the leg was one of the vascular changes observed in this study and was seen in 3 (1.2%) subjects during the first trimester, 50 (20.8%) subject in second trimester, and 85 (25.4%) subjects in the third trimester and none was seen in controls. Seven (2.9%), 23

(9.6%), and 27 (11.2%) subjects had palmar erythema in the first, second, and third trimesters respectively and only one (0.4%) in the controls. Varicosities of the legs were seen in 1 (0.4%) subject in first trimester, three (1.2%) subjects each in second and third trimesters and 1 (0.4%) in controls.

Nineteen (7.9%) subjects had pregnancy gingivitis mucous membrane changes) in first trimester, 28 (11.7%) and 29 (12.1%) subjects had it in second and third trimesters respectively and only one (0.4%) had it in controls.

Table 5b: Prevalence and pattern of other physiological skin changes in pregnancy and controls.

Skin changes Pregnant cases Controls n=240 N (%) First trimester Second trimester Third trimester N (%), N (%) N (%) 1. Hair changes Hirsutism 13 (5.4) 33 (13.8) 34 (14.2) 8 (3.3) Male-pattern 0 0 0 1 (0.4)

2. Nail changes Increased growth 43 (17.9) 94 (39.2) 89 (37.1) 4(1.7) Leuconychia 18 (7.3) 29 (12.1) 26 (10.8) 3(1.2) Nail fragility 3 (1.2) 13 (5.4) 12 (6.0) 2(0.8) Melanonychia 1 (0.4) 3 (1.2) 3 (1.2) 1(0.4)

3. Glandular Hyperhidrosis 16 (6.7) 55 (22.9) 59 (24.6) 3 (1.3) Heat rashes 6 (2.5) 11 (4.6) 8 (3.3) 11 (4.6) Acne vulgaris 84 (35.0) 100 (41.7) 85 (35.4) 58 (24.2)

4. Connective tissue

Striae 39 (16.3) 90 (37.5) 94 (39.2) 18 (7.5)

5. Vasculature Non-pitting edema 3 (1.2) 50 (20.8) 85 (25.4) 0.0 Palmar erythema 7 (2.9) 23 (9.6) 27 (11.2) 1 (0.4) Varicosities 1 (0.4) 3 (1.2) 3 (1.2) 1 (0.4) 6. Mucous membrane

Gingivitis 19 (7.9) 28 (11.7) 29 (12.1) 1 (0.4) N= Frequency

Majority of the pregnant women have more than one skin changes in pregnancy (Table 2).

6.7. PATTERN OF DISTRIBUTION OF STRIAE GRAVIDARUM IN SUBJECTS.

Figure 3 shows the pattern of distribution of striae gravidarum in pregnant subjects. Striae gravidarum located to the abdomen was the commonest anatomical site seen in 18 7.5) subjects in the first trimester, 44 18.3) and 39 16.3) subjects in second and third trimesters respectively. The breast also has more striae gravidarum with prevalence of 3 1.2), 9 3.8),

10 4.2) in first, second and third trimesters respectively. Striae gravidarum involving the abdomen, breast and arm together was the least common with prevalence of 1 0.4) each in all the trimesters.

Figure 3: Pattern of distribution of striae gravidarum

20 18.3 18 16.3 16

14 abdomen breast

12 thigh  buttock 10 abdomen and thigh

Frequency abdomen and buttock 8 7.5 abd+breast abd+breast+thigh 6 breast and buttock 4.2 3.8 abdomen+breast+arm 4 3.3 2.9 2.5 2.5 2.1 2.1 2.1 1.7 1.7 1.7 2 1.2 1.2 1.3 0.8 0.8 0.4 0.4 0.4 0.4 0 1st trimester 2nd trimester 3rd trimester Pattern of striae gravidarum

6.8 CLINICAL PATTERN OF MELASMA IN PREGNANCY AND CONTROL

Figure 4 depicts the clinical pattern of melasma in pregnancy and control. The most common clinical pattern of melasma is centrofacial and was seen in 12 5) subjects in first trimester, 18 7.5) and 17 7.1) subjects in second and third trimester respectively and only in

1 0.4) of controls. No malar clinical type was seen in first trimester, 4 1.7) were seen each in second and third trimester and 2 0.8) in control. No mandibular type was seen in this study.

Figure 4: Clinical pattern of melasma in pregnancy and control

8 7.5 7.1 7

5 5

 1st trimester 4 2nd trimester

3rd trimester Frequency 3 control

2 1.7 1.7

0.8 1 0.4 0 0 0 0 0 0 centrofacial malar mandibular Melasma in pregnancy

6.9 PREVALENCE AND PATTERN OF SOME OTHER DERMATOSES

Table 6 shows prevalence and pattern of some other dermatoses in pregnancy and controls.

Atopic dermatitis was the only inflammatory change seen in this study and was noticed in

1 (0.4%) subject each in first, second and third trimesters and none was seen in controls. The patient showed improvement of the disease during pregnancy.

Vaginal candidiasis was the most common skin infection and was seen in 44 (19.3%) subjects in first trimester, 57 (23.8%) subjects in second trimester and 53 (22.0%) subjects in

61 third trimester and only in 9 (3.8%) among the control population. Pityriasis versicolor both hypo- and hyperpigmented types, were the second highest skin infection in pregnancy and was observed in 11 (4.6%), 14 (5.8%) and 15 (6.2%) subjects in the first, second and third trimesters respectively and 3 (1.2%) in controls. Pityrosporum folliculitis was present in 4 (1.7%) subjects in first trimester and 7 (2.9%) subject each in second and third trimesters and none in control group.

Cutaneous tumour skin tags) localized to the neck area were observed in 3 (1.2%) subjects in first trimester, 5 (2.1%) subjects had it in second trimester, 4 (1.7%) subjects in third trimester and 4 (1.7%) in controls .

Pruritus located to the abdomen and breast was reported by 16 (6.7%) subjects in the first trimester, 85 (35.4%) subjects in the second trimester, and 116 (48.3%) subjects reported pruritus in the third trimester compared to 1 (0.4%) seen in controls.

Table 6: Prevalence and pattern of some other dermatoses in pregnancy and controls.

Skin changes Pregnant cases Controls n=240 N (%) First trimester Second trimester Third trimester N (%) N (%) N (%) a. Inflammatory Atopic dermatitis 1 (0.4) 1(0.4) 1 (0.4) 0.0

62 b. Skin infections Vaginal candidiasis 44 (19.3) 57 (23.8) 53 (22) 9 (3.8) Pityriasis versicolor 11 (4.6) 14 (5.8) 15 (6.2) 3 (1.2) Pityrosporum folliculitis 4 (1.7) 7 (2.9) 7 (2.9) 0.0 c. Cutaneous tumours Skin tags 3 (1.2) 5 (2.1) 4 (1.7) 4 (1.7) d. Miscellaneous dermatoses Pruritus 16 (6.7) 85 (35.4) 116 (48.3) 1 (0.4)

N= Frequency

Majority of the pregnant women have more than one skin changes in pregnancy (Table 2).

6.10 PREVALENCE AND PATTERN OF CLINICAL PRESENTATION OF ACNE

VULGARIS IN PREGNANCY.

Table 7 shows prevalence and pattern of clinical presentation of acne vulgaris in pregnancy.

Twenty (8.3%) subjects developed new lesions in first trimester, 15 (6.2%) subjects in second trimester, and 9 (3.8%) subjects in third trimester. Acne vulgaris in pregnancy was noticed to be worsened in 37 (15.4%) subjects in first trimester, 34 (14.2%) subjects in second trimester, and

26 (10.8%) subjects in third trimester. Improvement of pre-existing acne vulgaris in pregnancy was seen in 20 (8.3%) subjects in first trimester, 42 (17.5%) subjects in second trimester, and 44

(18.3%) subjects in third trimester. Seven (2.9%) subjects during the first trimester, 9 (3.8%) subjects in second trimester, and 6 (2.5%) subjects in third trimester had no change in their pre- existing acne vulgaris.

Table 7: Prevalence and pattern of clinical presentation of acne vulgaris in pregnancy.

Acne vulgaris Pregnant cases n=240

First Trimester Second Trimester Third Trimester N (%) N (%) N (%)

New lesion 20 (8.3) 15 (6.2) 9 (3.8)

Worsen 37 (15.4) 34 (14.2) 26 (10.8)

Improved 20 (8.3) 42 (17.5) 44 (18.3)

No change 7 (2.9) 9 (3.8) 6 (2.5)

N=Frequency

6.11 PREVALENCE AND PATTERN OF ANATOMICAL SITES OF PRURITUS IN

PREGNANCY

Figure 5 shows prevalence and pattern of anatomical sites of pruritus in pregnancy

Abdomen is the most common site of pruritus seen in 14 (5.8%) subjects in first trimester, 78

(32.5%) subjects in second trimester, and 108 (45.0%) subjects in third trimester. The breast is the second commonest location seen in 2 (0.8%) subjects in first trimester, seven (2.9%) subjects in second trimester, and 8 (3.3%) subjects in third trimester.

Figure 5: Prevalence and pattern of anatomical sites of pruritus in pregnancy

45 45

35 32.5

30  25 Abdomen

20 Breast Frequency 15

10 5.8 3.3 5 2.9 0.8

0 1st trimester 2nd trimester 3rd trimester Pattern of anatomical site of pruritus

6.12 ASSOCIATION BETWEEN SKIN CHANGES IN PREGNANCY AND

GESTATIONAL AGE.

Table 8a. Association between some skin changes in pregnancy and gestational age.

Table 8a-1displays the association between physiological skin changes and gestational age. Physiological skin changes was present in 185 (77.1%) and absent in 55 (22.9%) subjects in first trimester, present in 228 (95.0%) and absent in 12 (5%) subjects in the second trimester and present in 227 (94.6%) subjects while 13 (5.4%) subjects did not have it in the third trimester.

There was statistically significant association between physiological skin changes in pregnancy and increasing gestational age i.e. trimester (p-value= 0.000).

Table 8a-2 shows association between pigmentary changes and gestational age.

One hundred and eighty six (77.5%), 230 (95.8%), 229 (95.4%) subjects had pigmentary skin changes respectively in first, second and third trimesters while 54 (22.5%), 10 (4.2%) and 11

(4.6%) subjects did not have pigmentary changes. Pigmentary skin changes in pregnancy was statistically significantly associated with increasing gestational age (p-value=0.000).

Table 8a-3 shows association between presence of melasma and gestational age.

Twelve (5.0%) subjects had melasma while 228 (95.0%) did not have it during the first trimester,

22 (9.2%) had it in the second trimester while 218 (90.8) did not have it, in the third trimester 21

(8.8%) had melasma while 219 (91.2%) did not have it. There was statistically significant association between presence of melasma and increasing gestational age (trimester) (p- value=0.000).

Table 8a-4 shows the association between linea nigra and gestational age (trimester). Linea nigra was present in 61 (25.4%) and absent in 179 (74.6%) of subjects during the first trimester,

180 (75.0%) subjects had it while 60 (25.0%) subjects did not have it in second trimester, in the third trimester linea nigra was present and absent in 176 (73.3%) and 64 (26.7%) subjects respectively. There was no statistically significant association between linea nigra and increasing gestational age (trimester) (p-value=0.368).

Table 8a: Association between some skin changes in pregnancy and gestational age.

Skin changes Pregnant cases n=240 First trimester Second trimester Third trimester N (%) N (%) N (%) 1. Physiological Present 185 (77.1) 228 (95.0) 227 (94.6) Absent 55 (22.9) 12 (5.0) 13 (5.4) Total 240 (100.0) 240 (100.0) 240 (100.0)

2=58.0, df=2, p= 0.000 2. Pigmentary Present 186 (77.5) 230 (95.8) 229 (95.4) Absent 54 (22.5) 10 (4.2) 11 (4.6) Total 240 (100.0) 240 (100.0) 240 (100.0)

2 =80.5, df=2, p= 0.000

3. Melasma Present 12 (5.0) 22 (9.2) 21 (8.8) Absent 228 (95.0) 218 (90.8) 219 (91.2) Total 240 (100.0) 240 (100.0) 240 (100.0)

2 =16.6, df=2, p= 0.000

4. Linea nigra Present 61 (25.4) 180 (75.0) 176 (73.3) Absent 179 (74.6) 60 (25.0) 64 (26.7) Total 240 (100.0) 240 (100.0) 240 (100.0)

2 =2.0, df=2, p= 0.368

N=Frequency

Table 8b: Association between other skin changes in pregnancy and gestational age.

Table 8b-i shows the association between presence of acne vulgaris in pregnancy and gestational age. Acne vulgaris was present in 84 (35.0%) and absent in 156 (65.0%) of subjects during the first trimester, 100 (41.7%) subjects had it while 140 (58.3%) subjects did not have it in second trimester, in the third trimester acne vulgaris was present and absent in 85(35.4%) and

155 (64.6%) subjects respectively. There was statistically significant association between acne vulgaris and increasing gestational age i.e. trimester (p-value=0.018).

Table 8b-ii shows association between presence of non-pitting oedema and gestational age.

Non-pitting oedema was present in 3 (1.2%) and absent in 237 (98.8%) subjects in first trimester, it was present in 50 (20.8%) and absent in 190 (79.2%) subjects in the second trimester and in the third trimester it was present in 85 (35.4%) subjects and absent in 155 (64.6%) subjects.

There was no statistically significant association between non-pitting oedema in pregnancy and increasing gestational age i.e. trimester (p-value=0.223).

Table 8b-iii shows the association between skin infection in pregnancy and gestational age.

Fifty five (21.7%), 80 (33.3%) and 74 (30.8%) subjects had skin infection in first, second and third trimesters respectively while it was absent in 185 (78.3%) subjects during the first trimester, 160 (66.7%) subjects in second trimester and 166 (69.2%) subjects in third trimester.

There was statistically significant association between skin infections in pregnancy and increasing gestational age (p-value=0.000).

Table 8b-iv shows the association between striae gravidarum and gestational age.

Striae gravidarum was present in 39 (16.2%) and absent in 201 (83.8%) subjects in the first trimester, it was present in 90 (37.5%) and absent in 150 (62.5%) subjects in the second trimester, and in the third trimester it was present in 94 (39.2%) and absent in 146 (60.8%) subjects. There was statistically significant association between striae gravidarum and increasing gestational age (p-value=0.000).

Table 8b: Association between some other skin changes in pregnancy and gestational age.

Skin changes Pregnant cases n=240 First trimester Second trimester Third trimester N (%) N (%) N (%) i. Acne vulgaris Present 84 (35) 100 (41.7) 85 (35.4) Absent 156 (65) 140 (58.3) 155 (64.6) Total 240 (100.0) 240 (100.0) 240 (100.0)

2=8.0, df=2, p= 0.018 ii. Non-pitting oedema Present 3 (1.2) 50 (20.8) 85 (35.4) Absent 237 (98.8) 190 (79.2) 155 (64.6) Total 240 (100.0) 240 (100.0) 240 (100.0)

2 =3.0, df=2, p= 0.223

iii. Skin infection Present 55 (21.7) 80 (33.3) 74 (30.8) Absent 185 (78.3) 160 (66.7) 166 (69.2) Total 240 (100.0) 240 (100.0) 240 (100.0)

2=13.1, df=2, p= 0.000

iv. Striae gravidarum Present 39 (16.2) 90 (37.5) 94 (39.2) Absent 201 (83.8) 150 (62.5) 146 (60.8) Total 240 (100.0) 240 (100.0) 240 (100.0)

2=67.6, df=2, p= 0.000

N= Frequency

CHAPTER SEVEN

DISCUSSION

The general prevalence of pregnancy associated skin changes among primigravidae in this study was 88.3% in first trimester and 98.3% each during the second and third trimester and while a prevalence of 47.5% was found among the never pregnant control age match population.

The prevalence of skin changes among pregnant women varied widely. The prevalence of skin changes in pregnancy in previous studies was at least 3.6% for pregnancy specific dermatoses,

20.6% for other dermatoses affected by pregnancy and up to 100% for physiological skin changes in pregnancy.16 Rathore et al17, found a prevalence of 87.9% for physiological changes in pregnancy, Shah et al25 reported a prevalence of 90% with hyperpigmentation constituting

87.3%. Muzaffa et al38 a prevalence of 90.7%. Mashood et al3 reported prevalence of specific dermatoses in pregnancy to be 6.5%, while Chander et al18 5% of pregnancies, however they all used both primigravidae and multiparous women. These demonstrated that skin changes are common among pregnant women with similar prevalence in different populations. This might be explained by the enhanced pregnancy hormones, skin phototypes, racial differences and genetic factors.

Majority of the subjects in this study has more than one skin changes and the number of subjects with skin changes increased as pregnancy advanced. Some skin changes such as acne vulgaris, heat rashes and vaginal candidiasis improved between second and third trimesters which are responsible for the slight decline in prevalence during this period in subjects with more than one skin changes (Table 2).

The demographic profiles of the subjects in this study are similar to those of previous studies. The primigravidae enrolled into this study were 240 subjects (97 subjects in first trimester and 143 subjects in second trimester as in figure 2) and 240 never pregnant control populations. The age range found in this study was 18-40 years in both subjects and control groups. The mean age of pregnant subjects and non-pregnant control population were

27.53±3.88 years and 27.15±4.17 years respectively, This is similar to age range 18-40 years and mean age of 26.42 years reported by Rathore et al17, age range 18-36 years with a mean of 23 years reported by Kumari et al16, and mean age of 22.7 years with age range of 16-30 years reported by Sharath et al104 and Shah et al25 found age range 17-40 years with mean of 23 years.

This is in keeping with higher pregnancy rate among the younger age population possibly due to higher fertility rate in this age group. There was no statistically significant relationship between age, education, occupation and skin changes in pregnancy (p>0.05).

The prevalences of the three classes of skin changes in pregnancy in this study were higher than in controls. Physiological skin changes were higher than the other two classes of skin changes in pregnancy (Table 3). This is similar to findings in other studies where Rathore et al17 reported high prevalence of physiological skin changes in up to 87.6% of their patients. Sharath et al104 and Kumari et al16 also reported high prevalence of physiological skin changes in pregnancy in up to 93.9% and 100% of their patients respectively. The proportion of patients

71 with physiological skin changes were statistically significantly related to increasing gestational age (p<0.05). This study demonstrated that physiological skin changes are common among pregnant women compared to controls and that the prevalence increased as pregnancy advanced and this increase might be due to the upward trend of hormonal factors such as oestrogen and progesterone.

Some dermatoses affected by pregnancy have high prevalence in this study among subjects than in controls and the prevalence increased with increasing gestational age (Table 3). Kumari et al16 reported lower prevalence of 20.6% in a study in India possibly because the patients were not follow-up unlike in this study and of different races. The increasing prevalence noticed in this study was possibly due to rise in the levels of placental and ovarian hormonal effects as gestational age increased.

No case of pregnancy specific dermatoses was seen in this study during any of the three trimesters. This is similar to low prevalence reported in previous studies in which Chander et al18 studied 1430 pregnant women and observed that 5% of them had specific dermatoses of pregnancy while Masood et al3 and Raj et al37 found prevalence of 6.5% and 1.5% respectively.

The absence of any pregnancy specific dermatoses in this study demonstrated that specific dermatoses of pregnancy is very rare.6 This is probably due to the fact that this study was tertiary hospital based and majority of pregnant women do not present in tertiary health care facility but were often seen by private hospitals, traditional birth attendants, mission houses, primary and secondary health care facilities.

Pigmentary changes in pregnancy in this study had the highest prevalence of all the skin changes observed in all the trimesters while it was low in controls. The prevalence also increased as pregnancy advanced. In similar studies by Kumari et al16 and Rathore et al17 they documented

72 high prevalence of pigmentary changes in up to 91.4% and 85.9% respectively. There was statistically significant association between increasing gestational age (trimester) and pigmentary changes in pregnancy (p<0.05). This showed that pigmentary changes are common and more as the gestational age increases possibly due to increased secretion and activities of some hormones such as adrenocorticotrophic hormone ACTH), melanocyte stimulating hormone MSH) and cortisol which are known to induce hyperpigmentation.45 The higher prevalence in this study compared to Kumari et al16 and Rathore et al17 could be due to the fact that the patients were followed up to see those who developed skin changes in the later part of pregnancy unlike their studies where there were no follow up of the patients.

Nipple, areola hyperpigmentation and linea nigra were significantly higher than other pigmentary changes and showed increasing prevalence from first to third trimester. These findings are similar to previous study by Mahboobe et al48 where they documented high prevalence of hyperpigmentation in these normally pigmented areas. This is possibly due to high level of eostrogen, progesterone and probably greater population and more sensitivity of melanocytes to these hormones in these localized areas.45

Other pigmentary changes were generalized hyperpigmentation, accentuation of normally hyperpigmented areas such as the axillae, breast, nevi, and inner thigh. The other sites of increased localized pigmentation were seen over the abdomen, scar pigmentation and sun exposed areas face and neck). In this study, pigmentary changes were commonest in the third trimester, followed by second trimester and least in the first trimester. This is similar to the study by Neerja et al112 where it was observed that the skin changes in pregnancy were commonest in the third trimester, followed by second trimester and least in the first trimester. These demonstrated that pigmentary changes in pregnancy are common and it is directly proportional to the gestational age. This is probably due to increased output of some pituitary, placental and ovarian hormones such as -melanocyte stimulating hormone, progesterone, eostrogen, ACTH and cortisol.51

Pigmentary demarcation lines (Voigt’s lines) type B were seen in 0.4% of subject in first trimester, 2.1% and 4.2% in the second and third trimesters respectively. Type B Voigt’s lines coexisting with type A were each seen in 0.4% of the subjects in first, second and third trimesters respectively. No Voigt’s line was seen among the controls. Kumari et al16 reported

0.1% case with type B PDL of the 607 pregnant women studied in India. The higher prevalence of Voigt’s lines in this study compared to Kumari et al16 could be due to racial and skin type differences among various population and also possibly because the patients were not followed up in the previous studies to know who later developed PDL as pregnancy advanced. The possible explanation for the aetiopathogenesis of PDL was compression of peripheral nerves by the enlarged uterus in the late period of pregnancy, thus influencing the innervated cutaneous microvasculature to induce neurogenic inflammation with resultant pigmentation.34

Melasma was observed in few patients but still higher than the controls. The prevalence of melasma in pregnancy varied widely in previous studies. Kumari et al16 reported prevalence of

2.5% in a study of 607 pregnant women, Smith et al36 documented prevalence of 75%, Raj et al37 and Muzzafar et al38 reported 8.5% and 46.4% respectively. These variations might be due to skin phototype and effects of sun exposures in different climates. The most common clinical type was centrofacial in this study seen in up to 7.5 in second trimester possibly because this area has more melanocyte population than other sites and upon sun exposure potentiate tyrosinase activity and thus induce melanogenesis.45 Increasing gestational age (trimester) was significantly associated with increased prevalence rate (p<0.05). The lower prevalence in this study compared to Smith et al36 and Muzzafar et al38 is probably because pigmentation is less discernible in black skin than light complexion.16 Genetic predisposition and racial differences could also play a role in the prevalence of melasma in pregnancy. The pathogenesis of melasma has also been attributed to elevated oestrogen, progesterones, increased MSH levels and increased number of

74 melanocyte40 in some areas resulting in excessive deposition of melanin in the epidermis, dermal macrophages, or both.39, 40

Skin infections were common findings in this study with a higher prevalence in subjects compare to controls (Table 6). There was statistically significant association between skin infection and increasing gestational age (p<0.05). Among skin infections in pregnancy, vaginal candidiasis in this study had the highest prevalence compared to controls. More patients developed vaginal candidiasis as gestational age increased. In a similar study of 578 pregnant women in Imo state Nigeria, Akerele et al82 reported prevalence of vaginal candidiasis to be

20.4%, while Parish et al83 documented 10% in first trimester and 23% in third trimester, however both included multiparous women in their study. This study shows that skin infections are common in pregnancy possibly due to high level of hormone oestrogen which suppresses immunity and depressed cell mediated immunity in pregnancy.80 Glycosuria as a result of reduced renal threshold for glucose in pregnancy which favours the growth of candida species could also play a role. The proportion of patients with vaginal candidiasis were not statistically significantly associated with increasing gestational age p>0.05).

Pityriasis versicolor in this study was present in 4.6% in first trimester, 5.8% and 6.2% in second and third trimesters respectively. The controls had a prevalence of 1.2%. In a similar study by Zampino et al85, pityriasis versicolor in pregnancy had a prevalence of 5.7%. This shows that pregnancy increases the prevalence of pityriasis versicolor probably due to depressed cell mediated immunity in pregnancy.80 Genetic predisposition, sun exposure and moisture from increased sweating in pregnancy could also play a role.

The prevalence of nail changes was reported to be high in this study with more patients developing nail changes as pregnancy advanced compared to previous studies. Shah et al25

75 reported lower prevalence of nail changes among the 150 subjects in their study. Rathore et al17 also found lower prevalence of 2.1% among 2000 pregnant women studied. Increased growth was the most common nail changes reported in this study (Table 5b), similar to what was observed by Elling et al44 that nail growth is generally increased during pregnancy. Leuconychia was next in prevalence, followed by nail fragility and least prevalence was observed in melanonychia. Shah et al25 reported nail fragility in 3.3% and leuconychia in 1.3% which were lower than what was reported in this study while Mahboobe et al48 noticed a higher prevalence of nail fragility in up to 12.8%. This study demonstrated that nail changes are common in pregnancy possibly due to growth stimulating effect of pregnancy hormones such as oestrogen and increase blood flow to the nail bed as a result of increased blood volume in pregnancy. The reason for higher prevalence of nail changes in this study compared to Shah et al25 and Rathore et al17 could not be readily explained, but could be that the patients were followed up in subsequent trimesters to see those who reported nail changes in later part of pregnancy unlike previous studies where there were no follow up of the patients.

Hair changes were commonly reported among subjects in this study compared to controls. In a similar study by Muzaffa et al,38 hair changes were reported in 12.8% cases while

Shah et al25 documented 14.7%. Hirsutism was the commonest hair changes reported in this study and are higher than control population. The finding in this study is similar to that of

Mahboobe et al48 where they reported hirsutism to be the commonest hair change in up to 17.2% among 180 pregnant women studied. This study showed that hair changes are common in pregnancy and also increases as pregnancy advances. The reason for this could not be explained but could be attributed to the effect of upward trend of adrenocorticotrophic hormone,

76 adrenocorticosteroid secretion, ovarian androgen and oestrogen which prolong the anagen phase of the hair cycle as pregnancy advances.51

Hyperhidrosis was a common finding in this study compared to lower prevalence reported in controls. The prevalence was lower in this study than previous study. Prevalence of 75.5 was documented in a study in Iran.48 The higher prevalence in the Iran study compared to this study was probably due to warmer and dry desert climate in Iran which encouraged more sweating than this environment. The prevalence in this study is directly proportional to increasing gestational age and higher in subjects than controls. Hyperhidrosis has been linked to increased vasomotor activity in pregnancy resulting in excessive sweating from alteration in autonomic nervous system.49, 50 Also increased basal metabolic rate as a result of enhanced thyroid activity in pregnancy which favours increased sweating might play a role.

Acne vulgaris in this study has a higher prevalence compared to non-pregnant controls and previous studies. Kumari et al16 in India observed prevalence of acne vulgaris to be 2.4%. In another study of 140 pregnant women, Muzaffa et al38 reported pregnancy induced acne in

13.6% of cases, out of which 7.9% noted regression while 5.7% observed aggravation of their acne vulgaris. The lower prevalence in previous studies might be due to the fact that the patients were not followed-up. Pregnancy has unpredictable effect on acne vulgaris.38 Acne vulgaris may develop for the first time during pregnancy; preexisting acne may be exacerbated; or it may occasionally improve completely.44 During the first trimester, 8.3% each had acne vulgaris for the first time and improved in pregnancy, 15.4% and 2.9% of cases had worsening and no change of their pre-existing acne vulgaris respectively. In the second trimester, new acne vulgaris developed in 6.2%, 14.2% worsen, 17.5% improved and 3.8% had no change of their pre-existing lesions. The third trimester showed new appearance of acne vulgaris in 3.8%,

77 worsen in 10.8% of cases, improved in 18.3%, and 2.5% had no change in their pre-existing acne vulgaris. In a work by Mahboobe et al48, acne improved in 1.7% of cases, aggravated in 26.7% and remain without change in 47.4% of cases. The reason for these variations in outcome of acne vulgaris in pregnancy could not be explained but could possibly be due to differences in responses to stress of pregnancy. The improvement in acne could be due to therapeutic and beneficial effect of oestrogen.45 This study demonstrated that acne is not only common in pregnancy but also has unpredictable outcome during pregnancy. The proportion of patients with acne vulgaris showed statistically significant association with increasing gestational age

(p<0.05).

Striae gravidarum is common in this study and higher than the controls. It also increased in prevalence with increasing gestational age (trimester). A wide range of prevalence has been reported for striae gravidarum in previous study, 90%, 75%, 55%, 44.8% and 27.7% respectively by Muzaffa et al38, Raj et al37, Chang et al54, Kumari et al16 and Yamaguchi et al55. The variation in prevalence could be due to differences in races and genetic factors. Physical factors such as stretching of abdominal muscle from recurrent pregnancy in previous studies and advancing pregnancy could also play a role in these variations. Striae gravidarum has lower prevalence in blacks and primigravidae which may be responsible for the lower prevalence seen in this study.

16, 55 Increased adrenocortical activity, relaxin, oestrogen, distension and genetic predisposition were documented causes of striae gravidarum in previous studies.24, 51

Vasculature changes are commoner in this study with increasing pregnancy and compare to none in non-pregnant controls. Rathore et al17 observed a similar finding in 25.5% of 2000 pregnant women studied in India. The higher prevalence seen in this study in the second and third trimester is probably due to the fact that the patients were followed up to see those who

78 developed vascular changes at the last trimester. There was statistically significant association between vasculature changes and increasing gestational age (trimester) p<0.05.

Non-pitting oedema was the most common vasculature change seen in this study with increasing prevalence as pregnancy advanced and none was seen among the non-pregnant control population. In similar study by Kumar et al, 113 18% of subjects had pedal oedema. Nkwo

P65 documented prevalence of 8.5%. Kumari et al16 observed non-pitting pedal oedema in 9.8% while Muzaffa et al38 reported higher prevalence of 48.5%. There was no statistically significant association between non-pitting oedema and increasing gestational age (p>0.05). The higher prevalence in this study when compared to Kumari et al16 may probably be due to racial differences, relative anaemia and poor nutrition which is commoner in developing world.

Undiagnosed preeclampsia, renal and cardiac abnormality can also play a role.51 Previous studies have linked pedal oedema to increased capillary permeability, sodium and water retention secondary to enhanced adrenocortical hormones such as cortisol and ACTH in pregnancy.40, 49,

Additional aetiological factor is increased hydrostatic pressure in the blood vessels due to reduced venous blood return because of gravid uterus.45

The prevalence of palmar erythema was much higher than the controls and it increased with increasing gestational age.. In a similar study by Muzaffa et al38, it was seen in 12.1% of cases. Kumari et al16, reported no case of palmar erythema in their study of 607 pregnant India women possibly because their patients were not followed up to see those who developed palmar erythema with advancing pregnancy. Rathore et al17 observe palmar erythema in 18.7%. Bean60 documented that 62.5% of whites and 35% of blacks develop palmar erythema during pregnancy. This study showed that palmar erythema is common in pregnancy which could reflect hyperkinectic circulation, increased blood volume and flow in pregnancy. High levels of

79 circulating oestrogen causing angiogenesis and genetic predisposition could also explain palmar erythema in pregnancy.24, 51 The low prevalence in this study compare to Bean60 was probably due to less visibility of palmar erythema in darker skin. There was no statistically significant association between palmar erythema and increasing gestational age (p>0.05).

Varicosities were observed to have very low prevalence in this study (Table 5b) similar to previous studies. Raj et al37, documented varicosities in 0.5% out of 1,175 pregnant women,

Muzaffa et al38 reported prevalence of 2.8% while Rathore et al17 noticed varicosities in 3.2%.

The low prevalence of leg varicosities observed in this study may be attributed to maternal occupation as majority belong to active working class and not sedentary. Varicosities have been documented to result from blood vessels weakness, decreased soft tissue tone around the vascular wall and elevated venous pressure in femoral and pelvic vessels caused by gravid uterus.49, 51 Familial tendencies could also play a role.51

Pruritus was a common finding in this study with higher prevalence compared to controls.

The prevalence of pruritus in pregnancy increased from 6.7% in first trimester to 48.3% in the third trimester and only 0.4% in the controls. The prevalence varies widely in other previous studies. Wong et al98 observed pruritus unrelated to any pathology in 20% of cases, Kenyon

AP101 23%, Shivakumar et al102, 58.8% and Raj et al37, 73.6%. The reason for this variation could not be readily explained. The high prevalence of pruritus in pregnancy in this study when compared with that reported by Wong et al98 and Kenyon et al101 might be related to possible xerosis from excessive sweating, high humidity and subclinical pregnancy specific dermatoses of which all have pruritus as part of their symptoms.105, 108, 114 Pruritus located to the abdomen was the commonest in all the trimesters and increased in prevalence as pregnancy advanced (Figure

5). In a similar work by Kenyon et al101, pruritus of abdomen in pregnancy unrelated to specific

80 dermatoses of pregnancy was high and reported in 31% of cases. Pruritus on the breast was seen only in few patients. The higher prevalence noticed in pruritus located to the abdomen may probably be due to abdominal distension by the gravid uterus and more xerosis since abdomen is covered most of the time with clothing and sweating may be impaired.

The prevalence of atopic dermatitis was low in this study in all the trimesters, seen only in

0.4% each in first, second and third trimesters. Atopic dermatitis improved in this patient in all the trimesters. Vaughan et al70 reported prevalence of 36% among the 200 pregnant women studied. The reason for the low prevalence in this study could not be readily explained but may probably be due to lower prevalence in the general population in this environment compare to the industrialized nations. Genetic, environmental and lifestyle factors could also play a role.

Skin tags among pregnant subjects have low and similar prevalence as control population.

This is similar to the low prevalence of 3.3% documented in previous study by Rathore et al.17

Skin tags in pregnancy may probably be due to weight gain by pregnant women as it is a common finding in obesity.99 Familiar tendency4 and hormonal growth effect of high oestrogen level has also been linked to the development of skin tag in pregnancy mostly seen around the neck.24, 44

The only mucous membrane change noticed in this study was gingivitis. It has higher prevalence in subjects than control population. The prevalence also increased with advancing pregnancy. In similar studies by Shivakumar et al102, and Muzaffa et al38 they documented prevalence of 10% and 16.4 respectively. The aetiopathogenesis of pregnancy gingivitis is not known but might be linked to high level of progesterone, local irritation and nutritional deficiency.67

CHAPTER EIGHT

CONCLUSION AND RECOMMENDATIONS

CONCLUSION

This study has shown that the prevalence of skin changes among primigravidae is high in this environment and it was seen in 88.3% of the patients in first trimester, 98.3% each in second and third trimesters. Pigmentary changes were the highest skin changes seen in all the three trimesters and no specific dermatoses of pregnancy were seen in this study.

Genetic factors, hormonal factors, skin phototypes and racial differences might have played a vital role in the occurrence of skin changes in pregnancy.

RECOMMENDATIONS

This study demonstrated that skin changes are common among primigravidae in this environment. The following are thus recommended:

1. Every pregnant woman should undergo routine dermatological examination by trained

dermatologist at least once or as may be necessary during antenatal clinic to enable early

diagnosis and treatment of any skin changes that can affect the patient and her unborn

child.

2. Routine education about skin changes in pregnancy can be given by caregivers during

antenatal clinics to allay the fear about those skin changes that cause significant cosmetic

concerns to the patients.

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APPENDIX 1

PROFORMA

DEMOGRAPHIC DATA

(Kindly fill or check  as appropriate)

1. Serial Number ………………………………………………………….

2. Hospital Number………………………………………………………..

3. Age (years)……………………………………………………………….

4. Appointment Dates: 1st……………2nd…………….3rd………………..

5. Last Menstrual Period………………………EDD…………………….

6. Estimated Gestational Age…………… (Weeks). USS…………………

7. Number of Fetus (USS) :………………………………………………...

8. Marital Status: Single  Married  Cohabiting  Separated/ Divorce 

Widowed  Remarried  Others (specify):------

9. Educational Level: Nil  primary  Secondary  Tertiary 

Others ( specify):………………………

10. Maternal Occupation:…………...... Monthly Income:…………….

11. Husband Status: Civil servant  Self employed  Unemployed  Retired  Others

(Specify):……………………..Monthly Income:-………………….

12. Ethnicity/Race: Yoruba  Hausa  Igbo  Others(Specify):………………

13. Religion: Christianity  Islam  Traditional  None  Others (specify):………

14. Living Environment: Rural  Urban 

15. Symptoms Localised to the Skin

a. Pruritus Yes/No Duration:…………..

b. Rash Yes/No Duration:…………..

c. Blister Yes/No Duration:…………..

d. Pain Yes/No Duration:…………..

e. Increased skin colour Yes/No Duration:…………..

f. Reduced skin colour Yes/No Duration;………….

g. Others (Specify):…………………………………………………………….

16. Examination

a. Height………………………………..Meters ( M)

b. Weight………………………………..Kilogram (Kg)

c. BMI…………………………………..Kg/M2

d. Blood pressure………………………..mmHg

e. Pulse Rate……………………………..beat/min

f. Pallor…………………………………Yes No

g. Jaundice………………………………Yes No

h. Other (specify)………………………………….

CLINICAL DETAILS

Skin changes at each stage of pregnancy

17. Pigmentary changes 1st trimester 2nd trimester 3rd trimester

a. Hyperpigmentation yes no yes no yes no i. Generalized yes no yes no yes no ii. Nipple yes no yes no yes no iii. Areolae yes no yes no yes no iv. Breasts yes no yes no yes no v. Axillae yes no yes no yes no vi. Abdomen yes no yes no yes no vii. Inner thigh yes no yes no yes no viii. Sun exposed areas yes no yes no yes no ix. Melanocytic naevi yes no yes no yes no x. Scar yes no yes no yes no b. Voigt’s line (PDL) yes no yes no yes no c. Linea nigra yes no yes no yes no d. Hypopigmentation yes no yes no yes no e. Melasma yes no yes no yes no i. Centrofacial yes no yes no yes no ii. Malar yes no yes no yes no iii. mandibular yes no yes no yes no

f. Others(Specify):…………………………………………………………

18. Hair Changes 1st trimester 2nd trimester 3rd trimester

a. Hirsutism yes no yes no yes no b. Male-Pattern baldness yes no yes no yes no

c. Others(Specify): ………………………………………………………….

19. Nail Changes 1st trimester 2nd trimester 3rd trimester

a. Increased growth yes no yes no yes no b. Nail Fragility yes no yes no yes no c. Onycholysis yes no yes no yes no d. Leuconychia yes no yes no yes no e. Melanonychia yes no yes no yes no f. Hyperkeratosis yes no yes no yes no

g. Others(Specify): ……………………..…………………………………

20. Glandular Changes 1st trimester 2nd trimester 3rd trimester

a. Hyperhydrosis yes no yes no yes no b. Heat Rash yes no yes no yes no c. Acne Vulgaris yes no yes no yes no

d. Others(Specify):……………………………………………………….. 21. Connective Tissue Changes 1st trimester 2nd trimester 3rd trimester a. Striae gravidarum yes no yes no yes no b. Others(Specify): ……………………………..………………………………….

22. Vasculature Changes 1st trimester 2nd trimester 3rd trimester a. Spider angioma yes no yes no yes no b. Palmar erythema yes no yes no yes no c. Varicosities yes no yes no yes no d. Non –Pitting edema yes no yes no yes no e. Others(Specify)………………………………………………………………….

23. Cutaneous Tumours 1st trimester 2nd trimester 3rd trimester a. Pyogenic granuloma yes no yes no yes no b. skin tags yes no yes no yes no c. Others (Specify): ………………………………………………………………….

24. Mucus Membrane Changes 1st trimester 2nd trimester 3rd trimester a. Pregnancy gingivitis yes no yes no yes no b. Others(Specify)………………………………………………………………….

25. Infections 1st trimester 2nd trimester 3rd trimester a. Candidiasis yes no yes no yes no b. Pityriasis Versicolor yes no yes no yes no c. Pityrosporum folliculitis yes no yes no yes no d. Herpes zoster yes no yes no yes no e. Herpes Simplex Virus yes no yes no yes no

99 f. Genital Warts yes no yes no yes no g. Others (Specify)………………………………….………………………………..

26. Inflammatory Disorder 1st trimester 2nd trimester 3rd trimester a. Atopic Dermatitis yes no yes no yes no b. Psoriasis yes no yes no yes no c. Others(Specify)……………………..……………………………………………

27. Other Dermatoses 1st trimester 2nd trimester 3rd trimester a. Pruritus gravidarum yes no yes no yes no b. Acanthosis nigricans yes no yes no yes no c. Others(Specify) …………………………………………………………………..

28. Pregnancy–Specific Dermatoses 1st trimester 2nd trimester 3rd trimester a. Atopic Eruption of Pregnancy yes no yes no yes no b. Polymorphic Eruption of Pregnancy yes no yes no yes no c. Pemphigoid Gestationis yes no yes no yes no d.Intrahepatic Cholestasis of Pregnancy yes no yes no yes no

29. Laboratory Axis a. Pregnancy test: Positive  Negative 

100 b. Obstetric Ultrasound Scanning (USS):…………………………………………. c. Skin biopsy……………………………………………………......

…………………………………………………………………….. c. Skin scraping…………………………………………………………………. d. HIV Screening……………………………………………………………….. e. Urinalysis……………………………………………………………………… f. Others …………………………………………………………………………. …………………………………………………………………………. …………………………………………………………………………. ………………………………………………………………………….. …………………………………………………………………………..

30. Final dermatological diagnosis: - (I)………………………………………

(II)…………………………………………………………………………..

(III)………………………………………………………………………….

101

APPENDIX II

INFORMED CONSENT FORM

Serial Number: …………………......

In order to participate in this research study, it is necessary that you give your informed consent. By signing this informed consent form you are indicating that you understand the nature of the research study and your role in the research. and that you agree to participate in their research.

Please consider the following points before signing:

 I understand that I am participating in a research

 I understand that my participation will be anonymous and that all

information I provide will remain confidential.

 I understand that I will be provided with an explanation of the research

in which I participate.

 I understand that my participation in this research is voluntary and

that I may refuse to participate further at any time.

102

 I agree that investigations as outlined in the proforma can be carried

out on me by signing this form.

------

Signature/Thumbprint of Patients Signature of Investigator/Date

APPENDIX III

103

104

FIGURE 6: HIRSUTISM ON THE ABDOMEN

FIGURE 7: HIRSUTISM ON THE CHIN

105

FIGURE 8: LINEA NIGRA

FIGURE 9: SCAR HYPERPIGMENTATION ON THE ABDOMEN

106

FIGURE 10a: VOIGT’S LINES ON THE POSTERIOMEDIAL THIGH

FIGURE 10b: VOIGT’S LINES ON THE POSTERIOMEDIAL THIGH

107

FIGURE 11: NIPPLE, AREOLA AND BREAST HYPERPIGMENTATION

FIGURE 12: INCREASED NAEVUS PIGMENTATION ON THE RIGHT ARM

108

FIGURE 13: SKIN TAGS ON THE NECK AREA

FIGURE 14: STRIAE GRAVIDARUM ON THE ABDOMEN

109

FIGURE 15: PALMAR ERYTHEMA AT THE TIP OF THE FINGERS

FIGURE 16: MELANONYCHIA OF THE 2ND, 3RD AND 4TH FINGER NAILS.

110

FIGURE 17: BILATERAL PEDAL OEDEMA

FIGURE 18: LEG VARICOSITY ON THE LEG

111

FIGURE 19: PITYRIASIS VERSICOLOR ON THE ABDOMEN

FIGURE 20: ACNE VULGARIS ON THE FACE

112

113