“A Clinico Epidemiological Study on Dermatoses in Preterm Neonates”

“A CLINICO EPIDEMIOLOGICAL STUDY ON DERMATOSES IN PRETERM NEONATES”

Dissertation submitted in partial fulfilment of the Requirements for the degree of

M.D.(DERMATOLOGY, VENEREOLOGY & LEPROSY) BRANCH XX DEPARTMENT OF DERMATOLOGY MADRAS MEDICAL COLLEGE CHENNAI-600 003

THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY CHENNAI

MAY 2019

CERTIFICATE

This is to certify that the dissertation titled “A CLINICO EPIDEMIOLOGICAL

STUDY ON DERMATOSES IN PRETERM NEONATES” is a bonafide work done by Dr. VINITHA KUMARI. G, Post graduate student of the Department of Dermatology,

Venereology and Leprosy, Madras Medical College, Chennai – 3, during the academic year

2016 – 2019. This work has not previously formed the basis for the award of any degree.

Prof Dr. R. PRIYAVATHANI ANNIE Dr. MOHAMED SAJJID, MALATHY MD (PEAD), DM (NEONATOLOGY), M.D., D.D., D.N.B., M.N.A.M.S., Assistant professor of neonatology, Professor, Institute of Obstetrics & Gynaecology, Department of Dermatology, Women & Children Hospital, Egmore, Madras Medical College & Madras Medical College, Chennai - 3. Rajiv Gandhi Govt. General Hospital, Chennai-600 003.

Prof. Dr. U. R. DHANALAKSHMI Prof. Dr. R. JAYANTHI, MD.,DD.,DNB., MD., FRCP (Glasg). Professor and Head, Dean, Department of Dermatology, Madras Medical College & Madras Medical College & Rajiv Gandhi Govt General Hospital, Rajiv Gandhi Govt. General Hospital, Chennai-600 003. Chennai-600 003.

DECLARATION

The dissertation entitled “A CLINICO EPIDEMIOLOGICAL STUDY ON

DERMATOSES IN PRETERM NEONATES” is a bonafide work done by

Dr. VINITHA KUMARI. G, Department of Dermatology, Venereology and Leprosy,

Madras Medical College, Chennai – 3, during the academic year 2016-2019 under the guidance of Prof. Dr. R. PRIYAVATHANI ANNIE MALATHY, M.D., D.D., D.N.B.,

M.N.A.M.S., Professor, Department of Dermatology, Madras Medical College, Chennai -3.

This dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University,

Chennai towards partial fulfilment of the rules and regulations for the award of M.D Degree in Dermatology, Venereology and Leprosy (BRANCH – XX)

Prof Dr. R. PRIYAVATHANI ANNIE MALATHY, M.D., D.D., D.N.B., M.N.A.M.S., Professor, Department of Dermatology, Madras Medical College & Rajiv Gandhi Govt. General Hospital, Chennai-600 003.

DECLARATION

The dissertation entitled “A CLINICO EPIDEMIOLOGICAL STUDY ON

DERMATOSES IN PRETERM NEONATES” is a bonafide work done by

Dr. VINITHA KUMARI. G, Department of Dermatology, Venereology and Leprosy,

Madras Medical College, Chennai – 3, during the academic year 2016-2019 under the guidance of Dr. MOHAMED SAJJID, MD (PEAD), DM (NEONATOLOGY),

Assistant professor of Neonatology, Institute of Obstetrics & Gynaecology, Women &

Children Hospital, Egmore, Madras Medical College, Chennai -3.

This dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University,

Chennai towards partial fulfilment of the rules and regulations for the award of M.D Degree in Dermatology, Venereology and Leprosy (BRANCH – XX)

Dr. MOHAMED SAJJID, MD (PEAD), DM (NEONATOLOGY), Assistant professor of Neonatology, Institute of Obstetrics & Gynaecology, Women & Children Hospital, Egmore, Madras Medical College, Chennai - 3.

DECLARATION

I, Dr. VINITHA KUMARI. G, solemnly declare that this dissertation titled

“A CLINICO EPIDEMIOLOGICAL STUDY ON DERMATOSES IN PRETERM

NEONATES ” is a bonafide work done by me at Madras Medical College during

2016 - 2019 under the guidance and supervision of Prof. Dr. R. PRIYAVATHANI

ANNIE MALATHY, M.D., D.D., D.N.B., M.N.A.M.S., Professor, Department of

Dermatology, Madras Medical College, Chennai-600003.

This dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University,

Chennai towards partial fulfilment of the rules and regulations for the award of M.D Degree in Dermatology, Venereology and Leprosy (BRANCH – XX).

PLACE:

DATE: (Dr. VINITHA KUMARI. G)

SPECIAL ACKNOWLEDGEMENT

My sincere thanks to Prof. Dr. R. JAYANTHI, MD., FRCP (Glasg), Dean,

Madras Medical College, Chennai-3 for allowing me to do this dissertation and utilize the Institutional facilities.

ACKNOWLEDGEMENT

I am gratefully indebted to Professor and Head of the Department of

Dermatology, Prof. Dr. U.R. DHANALAKSHMI, M.D., D.D., DNB., for her invaluable advice, guidance and encouragement. She has been a source of constant motivation and support throughout the study. I am extremely grateful to her for guiding me throughout the study.

I would like to express my sincere and heartfelt gratitude to

Prof. Dr. S KALAIVANI M.D., D.V., Director and Professor, Institute of Venereology, for her kindness and support throughout the study.

I thank Prof. DR. ARASAR SEERALAR, MBBS., DCH., M.D (Paed)., Professor of Paediatrics, Head of the Department – Neonatology Unit, Institute of Obstetrics &

Gynaecology, Women & Children Hospital for his guidance, support and encouragement in completing my study.

I am grateful and thankful to my guide Prof. Dr. R. PRIYAVATHANI M.D.,

D.D., DNB., MNAMS., Professor of Dermatology for her guidance, support and encouragement in completing my study.

I also thank Dr. MOHAMED SAJJID, MD (PEAD), DM (NEONATOLOGY),

Assistant professor of neonatology, Institute of Obstetrics & Gynaecology, Women &

Children Hospital for his kindness, guidance, support and encouragement in completing my study.

I thank my Professor and Head of the department of Occupational and Contact

Dermatitis, Prof. Dr. S. NIRMALA M.D., for her help and support.

I thank Prof. Dr. A. RAMESH, M.D., D.D., DNB (DVL) Professor of

Dermatology for his priceless support.

I express my sincere gratitude to Prof. Dr. V. SAMPATH M.D., Professor of

Dermatology for his guidance and support.

I thank Prof. Dr. AFTAB JAMEELA WAHAB M.D., D.D., Associate

Professor of Dermatology for her advice and encouragement.

I wish to thank Prof. Dr. S.KUMARAVEL M.D., D.D., and

Prof. Dr. J. MANJULA M.D., DNB., former Associate Professor, Dermatology for theirs support and motivation.

I humbly thank my Co-Guide, DR. S.VENKATESAN MD., DNB., Assistant

Professor of Dermatology for his valuable guidance throughout my work. I would like to express my sincere and heartfelt gratitude for the time which he has devoted for my research project.

I extend my gratitude to Dr. R. MADHU M. D., D.C.H., Dr. V.N.S. AHAMED

SHARIFF M.D.D.V.L., B, VIJAYALAKSHMI MD (DVL),. Dr. R,MANIPRIYA

MD, DCh., Dr. K. DEEPA MD (DVL) , Dr. C.L. CHITHRA MD (DVL),

Dr. S. TAMILSELVI MDDVL, Assistant professors, Department of Dermatology for their kind support and encouragement.

I express my thanks Dr. SAMUEL JEYARAJ DANIEL M.D., Dr. K. UMA

MAHESHWARI M.D.D.V.L., my former assistant professors, Department of

Dermatology, for their support and help.

I also thank my STD Associate Professor Dr. VIJAYABHASKAR, M.D.D.V.L my Assistant Professors Dr. P. PRABAHAR, M.D.D.V.L., Dr. H. DHANASELVI,

M.D.D.V.L., Dr. K. GAYATHRI, M.D.D.V.L., Dr. T.VASANTHI M.D.D.V.L.,

Dr. E. BALASUBRAMANIAN, M.D.D.V.L., Dr. R. SNEKAVALLI M.D.D.V.L.,

Dr. T. VANATHY M.D.D.V.L., and Dr. C. DURGAVATHI M.D.D.V.L., DD.,

Institute of Venereology for their able guidance.

I express my thanks Dr. C. VIDHYA, M.D.D.V.L., Dr. R. HEMAMALINI,

M.D.D.V.L., my former assistant professors, Institute of Venereology, for their support and help.

I am thankful to my colleagues for their support throughout the study. I am also grateful to all paramedical staffs for rendering timely help to complete my study. I am also extremely thankful to my family for their motivation and encouragement. Last but not the least I am profoundly grateful to all patients for their cooperation and participation in this study. They have been the principal source of knowledge which

I have gained during the course of my clinical research.

CONTENTS

Sl. PAGE TITLE No NO.

1 INTRODUCTION 1

2 REVIEW OF LITERATURE 4

3 AIM & OBJECTIVES 49

4 MATERIALS AND METHODS 50

5 OBSERVATIONS & RESULTS 53

6 CLINICAL IMAGES 76

7 DISCUSSION 84

8 SUMMARY 91

9 CONCLUSION 93

10 BIBLIOGRAPHY

11 ANNEXURES

ABBREVIATIONS MASTER CHART KEY FOR MASTER CHART PROFORMA

INFORMATION SHEET CONSENT FORM ETHICS COMMITTEE APPROVAL CERTIFICATE PLAGIARISM DIGITAL CERTIFICATE

Introduction

INTRODUCTION

The skin is a complex and dynamic organ which performs numerous vital functions. The maturation process, starts at birth with the adaptation of skin to the relatively dry environment compared to in utero milieu. This adaptive flexibility results in the distinctive properties of infant skin. To deliver proper care to infant skin, it is necessary to appreciate that it is evolving with unique characteristics1.

Maturation of skin starts during embryogenesis through intercellular and intracellular signals among different tissue layers. Barrier function development increases with gestational age and the epidermal maturation is complete by 34 weeks of intrauterine life2.

During the skin barrier development, impaired function makes the skin susceptible to chemical damage, microbial infections and skin diseases, probably compromising the general health of the newborn. Preterm newborn, during the 1st weeks of life, has an even less developed skin barrier and therefore is even more at risk. Thus, it is exceedingly important to evaluate the risk of infections, topical agent absorption, skin barrier disruption and the risk of thermoregulatory failure.

Thus the skin of the preterm especially with low birth weight neonates is very delicate, immature, has weaker dermoepidermal attachment which place them at higher risk of systemic dissemination from cutaneous infections.

Most of the conditions develop more rapidly than in adults and are self- limiting. Although a host of the dermatoses in neonates is a result of physiological phenomenon and transitory, its recognition and distinction from life threatening conditions is necessary to allay parent’s anxiety and counsel them regarding its harmless nature. Some of the dermatoses or its variation in clinical presentation may be an earliest marker of certain life threatening conditions eg: X- linked hypohydrotic ectodermal dysplasia present initially in the neonatal period with scaling of skin.

Term- born after 37 completed weeks and before 42 weeks

Preterm-born before 37 weeks

Post-term-delivered after 42 weeks

Table 1: Structural and functional differences between infant and adult skin

Factors Infant Adult

“Epidermal thickness Thinner Thicker

Cell attachments and Less More epidermal cellularity

Dermoepidermal junction Flat Undulating

Lipids Less More

Melanin Less More

Water content Higher Lower

Natural moisturizing factor Lower Higher concentration

Trans epidermal water Higher Lower” loss

Review of Literature

REVIEW OF LITERATURE

CLASSIFICATION OF NEONATAL DERMATOSES

1) Physiological and transient conditions

2) Pathological conditions

. Oral lesions

. Ichthyotic disorders

. Pustular diseases of the newborn

. Congenital anomalies

. Hyperpigmented birth marks

. Hypopigmented birth marks

. Vascular lesions

. Blistering disorders

. Miscellaneous conditions

PHYSIOLOGICAL AND TRANSIENT CONDITIONS

Vernix caseosa

It is a whitish greasy cheese like substance which covers the skin of the newborn at birth. It is composed of dead epithelial cells, lipids and antimicrobial peptides. The covering is thick in term neonates, little over in premature infants and absent in post term neonates. It may cover entire skin or confined to body folds alone. It provides mechanical barrier to entry of pathogens via skin. Vernix acts as a biofilm and facilitates passage through birth canal. Its antimicrobial

4 property is due to presence of cathelicidin, psoriasin, defensins etc., which imparts antibacterial and antifungal properties3, 4. Its colour reflects intrauterine problems- yellow in case of hemolytic disease of the newborn and postmaturity, bile stained in fetal distress. The malodour of vernix may be the early sign of neonatal sepsis.

Rubor (erythema neonatarum)

It develops few hours after birth and seen in the central part of the body and it fades on its own in 24-48 hours postdelivery. This is due to decreased sympathetic tone at birth which leads to reflex vasodilatation and hyperaemic flush that appears bright red in colour. It resolves spontaneously and may be replaced by cutis marmorata5.

Acrocyanosis

Acrocyanosis or peripheral cyanosis is symmetrical and bilateral bluish discoloration of the palms, soles and around the mouth. It is a benign condition due to peripheral vasoconstriction, increased tissue oxygen extraction and accumulation of desaturated haemoglobin leading to cyanotic appearance5. It becomes more pronounced with hypothermia, polycythemia and hyperviscosity syndromes and improved by warming the extremities.

Cutis marmorata

It is a benign condition, where the skin appears reticulated or marbled with pinkish blue colour. This is a physiological response to cold temperature, but

5 some neonates develop faint marbling even under optimal environmental temperature. It is a transient phenomenon lasting for few minutes to hours. It should be differentiated from cutis marmorata telengiectatica congenita, a developmental capillary vascular malformation which is persistent in nature and may be associated with limb reduction anomalies, aplasia cutis congenita.

Harlequin colour change

It occurs in 15% of neonates, more common in preterm when compared to term babies. When the neonate lies on its side, upper half is pale and lower half of the body is deep red in colour6. Head, genitalia and mucosa are spared. It is transient and may last for few seconds to minutes. Differential diagnosis includes nevus flammeus and infantile hemangioma. Some speculated that it may reflect hypothalamic immaturity for the control of cutaneous vasculature tone.

Physiological jaundice (Icterus neonatorum)

It typically appears on the 2nd or 3rd day of life and peaks on 4th day, then gradually resolves. It is due to immature liver which cannot effectively remove bilirubin quickly from the circulation, leading to their raised levels in the blood. In premature babies it is more severe and has protracted course because of exaggerated red cell and hepatic immaturity.

Jaundice on day 1 or persistence beyond 10 days is pathological and one should think of infection, Rh incompatibility, liver diseases and Crigler Najjar syndrome7.

Pigmentary changes

This includes hyperpigmentation of external genitalia and linea alba which may last for two to three months. It occurs in 8% of newborn infants as a result of maternal and placental hormone influences.

Physiological scaling of the newborn

Superficial desquamation of skin is seen in 65% of the neonates. It is mostly confined to hand and feet, but may be widespread especially in postmature infants8. Ichthyosis vulgaris, X-linked hypohydrotic ectodermal dysplasia may be difficult to distinguish from physiological scaling, as these may also present with same clinical features in the neonatal period.

Differential diagnosis of desquamation at birth

1) Physiological desquamation

2) Postmature desquamation

3) Post inflammatory desquamation

4) Continual peeling skin syndrome

5) Ichthyosis vulgaris

6) X-linked ichthyosis

7) Lamellar ichthyosis

8) Congenital ichthyosiform erythroderma

Skin fragility

Skin of the neonate is thin and fragile, because of the weaker attachments between epidermis and dermis. When comparing preterm with term neonates, skin is very thin in preterm which may lead to increased transepidermal water loss and iatrogenic abrasions.

Lanugo hair

These are very thin, soft, unmedullated and usually unpigmented hair, which covers the entire body of newborn at birth. They are the first hair to be produced by the fetal hair follicles. It is shed during the eighth to ninth month of intrauterine life and replaced with 2nd coat of lanugo hair and thus more prominent in preterm babies. It can be seen everywhere on neonates’ body but more pronounced over shoulder and posterior trunk. These lanugo hairs are changed to vellus hair postnatally by the first month of life9. Hypertrichosis lanuginosa congenita is a pathological condition in which the body is covered with excess long lanugo hair with sparing of palms, soles and mucosa.

Neonatal occipital alopecia

During the 2nd trimester of fetal life, the scalp hair is shed synchronously and the regrowing hairs enter telogen phase in a wave form, from front to back at

8 around 12 weeks before delivery. After shedding of these telogen hairs, the hair follicle enter into anagen phase in a wave pattern from frontal to occipital area, but the occipital hair follicles do not enter the telogen phase until term and therefore rather discernible alopecia may appear in this site that is termed as neonatal occipital alopecia10, 11, 12.

Sebaceous gland hyperplasia/ hypertrophy

This is a common benign disorder of the sebaceous glands. It is seen in more than 50% of neonates and occurs less commonly in preterm babies. It is slightly higher in male infants. They present as multiple uniform pinpoint yellow or white papules on nose, cheeks, upper lip, forehead and also on chest, areola, genitalia and limbs. It results from the action of maternal androgens on the pilosebaceous follicles with resultant increase in sebaceous gland number and volume. Histology shows large sebaceous gland and prominent secretory cells13. It resolves on its own after few months of delivery.

Milia

It is a common physiological finding on the face in 40% of neonates. These are miniature follicular epidermal cyst14. They present as tiny pearly white 1-3 mm sized globular papules on the nose, cheek, forehead, chin and scalp region.

The numbers of lesions vary from few to many hundreds. Large solitary milium may occur on areola, foreskin and scrotum or labia majora. Histologically the cyst

9 has a stratified squamous epithelium with a granular layer and central lamellated keratin15.

Extensive, persistent or abnormally located milia may be associated with type 1 Orofacial digital syndrome, Pachyonychia Congenita, Marie Unna type congenital hypotrichosis and X-linked Bazex-Dupre-Christol syndrome.

Miniature puberty

This is due to the effects of maternal and placental hormones on the reproductive organs of newborn giving rise to a number of conditions16. It presents as enlarged clitoris, mucoid vaginal discharge, enlarged well-formed genitals, hypertrophied mammary glands and they resolve in 2- 4 weeks. There may also be frank withdrawal bleeding on day 3 or 4 which lasts for two to three days. Galactorrhoea in the newborn called as witch’s milk may also be seen on day 2 or 3.

Erythema toxicum neonatorum

It is also called toxic erythema of the newborn. It is seen in approximately

1/ 3rd of newborns. The incidence is less in preterm and small for date babies.

There is no sex predilection. It starts after 24 - 72 hours after birth and disappears rapidly in 3 - 4 days.

The characteristic lesions are red macules, sometimes with small pustules distributed over the trunk, face and proximal part of extremities especially thighs;

10 however can occur at any site except palms and soles. There may be associated peripheral blood eosinophilia. The exact cause is not known. Histopathology shows subcorneal pustules with eosinophils, in relation to pilosebeceous follicle.

Smears from the pustule shows inflammatory cells of which 90% of cells are eosinophils. It is one of the differentials for sterile pustule. Apart from reassuring the parents, no treatment is needed.

Miliaria crystallina (sudamina)

Miliaria crystallina arising as a result of blockage of eccrine duct at the level of stratum corneum. It is equal among sexes and races, seen in first few weeks of life. It is located superficially when comparing miliaria rubra. Clinically it presents as crops of asymptomatic thin walled clear vesicles of size 1-2 mm without associated erythema and rupture within a day, followed by bran like desquamation. It is seen mostly on the forehead, scalp, neck and upper part of trunk and proximal extremities. Treatment is same as miliaria rubra, like the removal of predisposing aetiological factors.

Miliaria rubra (prickly heat)

This is a condition resulting from blockade of eccrine sweat duct deeper in the epidermis. It is seen in the first few weeks of life and involves both sexes equally. It lasts for hours to days. It presents as crops of erythematous papules most often in flexures like neck, axilla and groin. It can be widespread with the involvement of face, scalp, trunk and extremities. Histological examination shows

11 intraepidermal spongiosis and vesicles associated with sweat ducts. It improves once the predisposing factors like high heat, humidity and occlusion are removed.

Topical calamine lotion can be applied for the soothening effect.

Transient neonatal pustular melanosis

It involves 5% of the newborns and more common in black neonates. It is actually a variant of erythema toxicum neonatorum. Lesions are superficial, fragile pustule measuring 1-3 mm with no surrounding erythema and usually present at birth. They favour chin, neck forehead, palm, sole and buttock but can involve any site. They desquamate leaving brown macules which may persist for about 3 months. Smear from the pustule shows neutrophils and rarely eosinophils.

No organism is demonstrable. Pathology shows intra and subcorneal neutrophils with few eosinophils and macules demonstrate basilar and suprabasilar hyperpigmentation, treatment is not needed as it is a self-limiting phenomenon.

Sucking blisters and erosions

These are oval shaped blisters or erosions present at birth, resulting from vigorous sucking in utero. They can be seen on the fingers, upper lip, wrist, forearm and rarely foot. They heal spontaneously by 2 weeks of age without any residual sequelae. These may be confused with impetigo, herpes infection and cutaneous mastocytosis.

Epstein pearl

Epstein pearl is seen in about 85% of the neonates. These are microkeratocyst of 1-3 mm diameter, yellowish white in colour, located on the median palatal raphe. It has no gender predilection. They develop as a result of entrapment of epithelial cells in the fusion line of alveolar processes. They disappear within few weeks of life without any intervention.

Bohn’s nodules

It is an inclusion cyst, occurs more on the alveolar ridge of maxilla than the mandible. They are firm, 3mm greyish white nodules. The common differential diagnoses are dental laminar cyst, natal teeth and large epstein pearl. Most of them resolve spontaneously.

Sucking pad or sucking calluses

It present as painless whitish swelling of epithelium of lips due to the sustained sucking effort of newborn. It is due to the combined effect of intracellular edema and hyperkeratosis of the mucosa. It usually resolves once the breastfeeding is stopped.

PATHOLOGICAL CONDITIONS

Oral lesions in newborn

Ranula

Ranula is the mucous extravasation or retention cyst of the sublingual salivary gland. It is of 3 types. The first variety is superficial or oral Ranula that presents as a bluish cystic lesion on the floor of oral cavity. The second type called the cervical or deep plunging ranula is seen as swelling in the upper part of neck due to extension below the mylohyoid muscle17. Third variety is occurence of both type 1and 2 together in the neonate. It may remain asymptomatic or interfere with feeding and thus require intervention by aspiration, marsupialization or excision of the cyst18.

Other oral lesions are gingival or dental laminal cyst, succulent gums,

Leukoedema, congenital epulis, natal teeth, lymphangioma of alveolar ridge, hemangioma, eruption cyst, median alveolar notch, epidermoid and dermoid cyst.

ICHTHYOTIC DISORDERS

Collodion baby (lamellar desquamation)

Collodion baby is a distinct clinical entity in which neonate’s entire body is covered with shiny taut parchment like membrane. Its incidence is 1 in 100,000 deliveries19. It is the early manifestation of various types of ichthyoses of which lamellar ichthyosis and nonbullous ichthyosiform erythroderma are the most common20, 21.

Table-2: Causes of collodion baby22

“Percentage Causes Autosomal recessive congenital ichthyoses

75% a) Lamellar ichthyosis b) Congenital ichthyosiform erythroderma Other keratinization disorders a) AEC syndrome b) Chondrodysplasia punctata c) Gaucher disease d) Loricrin keratoderma e) Neutral lipid storage disease

15% f) Sjogren–Larsson syndrome g) Trichothiodystrophy h) X-linked hypohydrotic ectodermal dysplasia i) Others-Ichthyosis Vulgaris, congenital hypothyroidism, Chanarin Dorfman syndrome, Ichthyosis Variegata, Ketoadipiaciduria, Koraxitrachitic syndrome

10% Self-healing collodion baby”

The affected infant has ectropion, eclabium, fish like mouth, flattened nose and ears, claw like hands and limited joint mobility. Loss of part of the digits may occur due to its interference with blood flow. Within hours, it dries and cracks & bleeding occurs along the lines of fissure. After 24 to 48 hours it starts peeling off either in extensive sheets or as large brown scales, but after sometimes, it reforms again and the process continues.

Due to tight skin on thorax, respiration may be interfered and infrequently respiratory distress may result from nasal obstruction. Other complications are temperature dysregulation, fluid and electrolyte imbalance, hypernatremic dehydration, septicaemia, and acute renal shutdown23, 24.

Management includes frequent emollient application, maintenance of adequate hydration, electrolytes & nutrition and prophylactic antibiotics for prevention of infection25.

Harlequin ichthyosis

It is the most severe form of congenital ichthyosis. The inheritance is autosomal recessive, but many cases are sporadic and it is lethal in 44% of cases.

The infant is covered with armour like skin, which impairs movement and interferes with feeding and breathing. Due to thick rigid hyperkeratotic skin, there is ectropion and eclabium. Autoamputation of digits develop in 10% of infants26.

The major cause of death is sepsis from deep fissures, pneumonia and respiratory compromise from mechanical restriction of breathing. Treatment is like collodion baby with emollients, maintaining adequate hydration, electrolytes & nutrition etc.

PUSTULAR DISEASE OF THE NEWBORN

It is divided into infectious and non-infectious etiology27.

“Infectious causes a) Bacterial:

 Bullous impetigo

 Folliculitis

 Congenital syphilis

 Listeriosis

 Ecthyma (Staphylococcus aureus)

 Ecthyma gangrenosum (Pseudomonas aeruginosa)

b) Viral

 Neonatal herpes and congenital herpes simplex

 Neonatal varicella

 Cytomegalic inclusion disease

 Congenital Epstein-Barr virus syndrome

c) Fungal

 Congenital candidiasis

 Neonatal candidiasis

 Pityrosporum folliculitis

17 d) Parasites

 Scabies

Non-infectious causes

a) Miliaria pustulosa or profunda

b) Transient benign neonatal pustules

- Erythema toxicum neonatorum

- Transient neonatal pustular melanosis

c) Infantile acropustulosis

d) Benign cephalic pustulosis

e) Neonatal acne

f) Incontinentia pigmenti

g) Neonatal Langerhans cell histiocytosis

h) Transient myeloproliferative disease in patients with Down syndrome

i) Eosinophilic pustular folliculitis

j) Eosinophilic papular-pustular rash of Hyper IgE syndrome

k) Eosinophilic pustulosis

l) Neonatal Behcet’s disease

m) Neonatal pustular psoriasis”

Eosinophilic pustular folliculitis

It is an idiopathic inflammatory pustular disorder of the infants with associated cutaneous and peripheral blood eosinophilia. Age of onset is from birth up to 1st year of life and is predominant in male babies. It clinically presents as

18 recurrent crops of itchy sterile pustules on scalp primarily, with some lesions on trunk and extremities. There may be cervical, axillary or inguinal lymphadenopathy. It resolves spontaneously, without scarring. Smears and culture for microorganisms are negative. Tzanck smear shows abundant eosinophils.

Because of the self-limiting nature, treatment is not indicated. However in extensive and recalcitrant disease, topical steroids and tacrolimus and dapsone may be useful 28.

Acropustulosis of infancy

This is a rare disorder of unknown etiology presenting with recurrent crops of intensely pruritic vesicles and pustules distributed predominantly over the soles and palms on both the surfaces and it heals with post inflammatory hyperpigmentation. Treatment options are potent topical corticosteroids, maxacalcitol and dapsone in severe cases 29, 30, 31.

Congenital candidiasis

It is a rare disease with less than 1% incidence. The condition usually presents at birth or within a week after delivery. It is due to maternal chorioamnionitis resulting from transplacental or ascending infection from birth canal. Transplacental infection is rare but may be severe with the liver most frequently affected. The neonate presents with diffuse, generalized pustules on erythematous base with palmar and plantar pustules, considered as the hallmark of the disease. Bulla may develop rarely. Onychia and paronychia can also develop,

19 but mucosa and napkin area are spared. Systemic involvement is heralded by scalded or burn-like appearance of cutaneous lesions. Due to aspiration of infected amniotic fluid, involvement of respiratory and gastrointestinal tract may occur.

Candidal septicemia manifests as bronchopneumonia, microabscesses in liver, spleen, brain and kidney, endocarditis, meningitis and arthritis. Diagnosis is by simple KOH examination of skin lesions, showing pseudohyphae and budding yeast. Treatment includes both topical and systemic antifungal therapy32.

Amphotericin-B is considered as the first line drug for congenital candididasis at a dose of 0.5 to 1 mg/kg/day for a minimum period of 21-28 days33.

Neonatal candidiasis

Candidal infection is more common in preterm and extremely low birth weight (less than1000) neonates. It occurs after the first week of life and lasts for

2 weeks. They have pink to red macules and papules evolving into pustules and vesicles, involving the oral mucosa and diaper area. Pseudohyphae and spores are demonstrable from pustule on KOH mount examination. It is treated with topical nystatin, clotrimazole or miconazole for 10 days.

Impetigo neonatorum

It is bullous impetigo of neonates, caused by staphylococci. The age of onset is between 2nd day and 2nd week of life. It presents as red papules and clear blisters on an erythematous base involving cheeks, neck, inner thighs and diaper area. The bulla is superficial and heals without scarring34. Gram staining of

20 blisters shows gram positive cocci in clusters and polymorphs. Treatment involves local wound care, topical and systemic antistaphylococcal antibiotics, depending on the clinical severity.

Neonatal scabies

Scabies is rare in neonates. It manifests as vesicles, papules, pustules and rarely burrows involving the cheeks, hands, feet and trunk region. It is contracted from parents or persons handling the neonate. Diagnosis is mostly clinical, rarely requires demonstration of mite in mineral oil mount. Treatment is by 5% precipitated sulfur in petrolatum as other antiscabeitic drugs are contraindicated in the neonatal period.

Bacterial sepsis

Bacterial sepsis is more common in preterm than full term infants. The pustules are discrete, of size 1-9 mm with a red base. Newborns have poor feeding, lethargy, irritability or drowsiness and may be associated with signs of jaundice, pallor, cyanosis, petechiae, hepatosplenomegaly and hypothermia. It progresses rapidly within hours and mortality is high, if not recognized at the earliest.

Neonatal congenital syphilis

The clinical presentation is variable. At birth infants may be asymptomatic

(60%) or have life threatening infection. The common manifestations are mucocutaneous lesions (40-50%), hepatosplenomegaly (40-70%), bone involvement (78%), low birth weight (50%), lymphadenopathy, pneumonia, rhinitis often blood stained, nephritis, enteritis, pancreatitis and hematological abnormalities may be present35, 36.

The skin is usually normal at birth. Lesions appear between 2nd and 8th week usually and occasionally later. It tends to involve face, palms, soles and anogenital area. There may be macules, papules, papulosquamous, vesicles, pustules, erosions or ulcers. Infants may also have paronychia, desquamative gingivitis, condylomata lata in the anogenital and other flexural areas. As the syphilis strikes back, congenital syphilis is on the rise.

Neonatal HIV disease

HIV transmission from mother to child can occur in-utero, during labour or in the postnatal period through breastfeeding. In the absence of any preventive strategies, the overall risk of transmission is between 15 and 25% in developed countries and up to 45% in South East Asian region. The risk is around 10-15% in both antepartum and postpartum period. The majority of transmission occurs in intrapartum period which is 65 to 75% via direct contact with infected blood and

22 cervicovaginal secretions. Transmission may also be due to transplacental micro transfusion as the placental integrity is disrupted during labour.

There is no specific feature unlike other congenital syndromes in HIV positive neonates. The major problem lies in diagnosis, as the maternal antibodies persist in the circulation for about a period of 7 months. Thus HIV status of the infant up to 18 months of age should be determined by DNA-PCR. After 18 months of age antibody tests like ELISA can be applied for the diagnosis.

The cutaneous manifestations include oral thrush, impetigo, herpes, molluscum, wart, scabies, Cryptococcus, sporotrichosis, histoplasmosis, seborrhoeic dermatitis, psoriasis, eczema and drug eruption. All the infected neonates should be followed carefully to allow early identification and treatment of infection37.

Congenital anomalies

In general, congenital anomalies are classified into three types namely

1) Disruptions

2) Deformations

3) Malformations

Disruptions:

It is a rare anomaly related to interruption of the normal foetal developmental process, e.g. craniofacial cleft resulting from amniotic bands.

Deformations:

These result secondary to mechanical forces leading to anomalies of lesser degree, when comparing disruption eg. club foot, cleft palate, Pierre Robin sequence etc.

Malformations:

The morphologic defect in an organ arises from an intrinsically abnormal developmental process. Examples are polydactyly, congenital heart anomalies, cleft lip etc.

Accessory tragi

They are relatively common congenital abnormality, with an incidence of

1-10 per 1000 live births. They are also referred to as heterotrophic tragi or supernumerary tragi. Often, they are inaccurately labeled as preauricular skin tags, accessory auricle, polyotia, rudimentary ear and supernumerary pinna. It typically presents as pedunculated or sessile, skin-coloured papules or nodules located in the preauricular region. They are mostly solitary and unilateral, but can be multiple and bilateral. They might feel soft or firm on palpation which depends on the degree of underlying cartilaginous structure.

They are a constant finding in oculoauriculovertebral dysplasia (Goldenhar syndrome) and also been associated with hearing impairment and renal abnormalities such as hydronephrosis and horseshoe kidney in small number of cases.

Treatment might be sought if it is cosmetically unacceptable or if there is localized irritation. Complete surgical excision by a plastic surgeon is warranted.

Care must be taken to remove all the underlying cartilage, as incompletely excised cartilage may get infected and delays wound healing.

Abnormalities of lip and mouth

These include Pits or sinuses in the lip, clefting of lip and the palate.

Majority of the orofacial clefts are non syndromic. Associated anomalies were more common in newborn with cleft lip and palate (32%) than in babies with cleft lip (11%) or palate alone (22%). It may be associated with anomalies in other organs like eye, ear, heart, upper limb, lower limb, genitals, mandible, skull, tongue, skin and hair. Syndromes associated are Van der Woude Syndrome, Pierre

Robin syndrome and Velocardiofacial syndrome.

Amniotic constriction band

This is a rare clinical entity with varied manifestations that ranges from isolated malformations to combination of congenital malformations. The etiology of this entity is unknown. Both the genders are equally affected. Most of the cases are sporadic in occurrence. Auto-amputation of the digits or extremities may also develop as a complication.

Epicanthal fold

It is fold of skin on the inner aspect of eye. It is frequently observed in

Down’s and Klinefelter’s syndrome.

Digital abnormalities

Simian crease is single transverse crease that extends across the palms. It is seen most commonly in Down’s syndrome, but also noticed in Patau syndrome,

Cornelia de lange syndrome, Seckel’s syndrome and Cri du chat syndrome.

Clinodactyly is deviation of a finger in radioulnar plane away from the axis of joint flexion-extension. It is observed in Down’s, Aarskog and Seckel syndrome. It has also been reported to be associated with keratosis palmaris et plantaris. Syndactyly refers to partial or complete fusion of the fingers or toes.

Foot abnormalities like polydactyly, rocker deformity, congenital vertical talus and club foot may also occur.

Neural tube defects

These are anomalies of neurulation during the fetal development. They are broadly classified into cranial and spinal defects. The cranial defects are further categorized into encephalocele, anencephaly and inencephaly.

Anencephaly is further subdivided into meroanencephaly and holoanencephaly.

The spinal cord defects are classified into open and closed neural defects. Open variety includes myelocele and meningomyelocele. Closed type includes meningocele and spina bifida occulta38. A tuft of hair called faun tail nevus overlies an occult spina bifida, nowadays its incidence has come down as a result of routine folate supplementation in the antenatal period.

Skin dimpling

Neonates may have dimple like depressed scars primarily or due to injury from amniocentesis39.

Focal dermal hypoplasia

It is also called Goltz syndrome. It is a rare syndrome characterized by dermal thinning that leads to fat herniation with cutaneous and systemic abnormalities. Inheritance is X linked dominant, thus lethal in male babies. It has wide range of clinical features having developmental skin defects with ocular, dental and skeletal anomalies.

Skin involvement is considered essential for the diagnosis of Goltz syndrome, other cutaneous manifestations are raspberry like papillomas around mouth, ears and perineum.

Telangiectasia may also occur. Dental anomalies include malocclusion, hypoplastic irregular dentition, absent teeth, enamel defects, and slow eruption of defectively formed teeth.

Skeletal defects are the 2nd most common extracutaneous abnormalities, seen in around 80%40 of the neonates which include asymmetrical involvement of hands and feet with syndactyly, polydactyly or clinodactyly. Vertebral anomalies like scoliosis, kyphosis, vertebral body fusions and spina bifida may also be seen.

Management includes multidisciplinary approach involving orthopaedician, ophthalmologist, dentist, pediatrician and dermatologist. Cryotherapy and pulsed dye laser may be used to treat papillomas and telangiectasia.

Aplasia cutis congenita

It occurs in 1 in 1000 live births. It is dominantly inherited heterogenous group of disorders in which focal absence of skin is a common characteristic.

Here there is failure of formation of layers of skin like epidermis, dermis and fat altogether or a single layer alone is missing.

At birth it manifests as an ulcer, erosion or a scar. It commonly involves scalp near the parietal hair whorl. The size ranges from 0.5 to 10 cm. it may be circular, oval, linear or stellate in shape. 25% of cases have more than 1 lesion. In scalp lesion the defect may extend down into the dura. It is classified into 9 types.

Types Associated features

1 without any associated anomalies 85% of cases

2 With limb anomalies

3 With epidermal nevus

4 With other embryonal defects

5 With fetus papyraceus or placental infarct

6 With epidermolysis bullosa

7 Localised to limbs

8 Caused by teratogens

9 Associated with syndromes

Differential diagnoses are forceps injury, congenital herpes simplex and varicella infection, congenital syphilis, epidermolysis bullosa and Goltz syndrome. Histology shows atrophy of epidermis and dermis with absence of adnexal structures. Supportive care alone is sufficient in most cases as it heal on its own. Larger lesions (more than 4 cm) and persisting lesions may need surgical grafting to prevent complications like meningitis, haemorrhage and thrombosis.

Nevus Sebaceous of Jadassohn

It represents a circumscribed harmartomatous lesion composed of excess sebaceous glands. It occurs in 0.3% of newborn. It is mostly present at birth and scalp is the common site.

It has 3 stages-

1st stage manifests as flat or slightly raised greasy oval or linear area of yellow to orange discolouration. On scalp, it presents as hairless patch as the hair follicles are rudimentary. During the 2nd stage it becomes hyperkeratotic verrucous and nodular due to androgen stimulation. Various benign and malignant neoplasms develop from it in the 3rd stage. It may present as an isolated entity or part of epidermal nevus syndrome. Treatment of choice is surgical excision just prior to puberty.

Table 3: MIDLINE FACIAL LESIONS

Sl Tumour Clinical features no: Solid, mobile, skin coloured, non-pulsatile mass may 1 Dermoid cyst have hair, trans-illumination negative Blue, soft, pulsatile, compressible tumour, may 2 Encephalocele transilluminate, enlarges with crying Red-blue, mobile, firm tumour, non-pulsatile, non- 3 Nasal glioma compressible, trans-illumination negative Hemangioma 4 Red-blue, mobile, non-compressible tumour

5 Epidermoid cyst Mobile, skin to yellow coloured cystic mass

Firm, fixed tumor, irregularly shaped and skin colored 6 Infiltrative tumor

Vascular malformations, polyps, Mucocele, fibromas, 7 Others lipomas, fibromyxomas, granulomas

HYPERPIGMENTED BIRTH MARKS

Cafe-au-lait macule (CALM)

Cafe-au-lait macule is a well circumscribed, uniformly light to dark brown macule or patch. They are benign birthmarks but however, they may also be markers of certain systemic diseases. Size of the lesion ranges from 2 mm to a maximum of 20 cm and located on trunk and extremities. Histology shows increased epidermal melanin but melanocyte number is normal. The associations are numerous some of them are neurofibromatosis, Legius syndrome, tuberous sclerosis, Fanconi anemia, Ataxia telangiectasia, Silver–Russell syndrome, Bloom syndrome etc.

Lentigines

These are poorly circumscribed hyperpigmented round or oval macules of size 2-5 mm. They are predominantly located on sun exposed areas. They do not fade away in the absence of sun exposure. Syndromes associated with lentigines are Peutz–Jeghers syndrome, PTEN harmartomatous syndromes, Carney complex,

Lentiginoses and LEOPARD syndrome.

Speckled lentiginous nevus

These are also called as spotty nevus and speckled nevus spilus. These are either congenital or acquired, consisting of a large light brown patch, containing numerous small dark brown macules or papules. It may be seen anywhere on the body, but the most common site is on the chest and upper limbs.

Size ranges from 5 mm-10 cm. The histological patterns of the colored base are those of a simple freckle or cafe-au-lait patch, while the spotted macules are usually made up of junctional, compound or intradermal nevi41.

Linear and whorled nevoid hypermelanosis (LWNH)

LWNH presents as hyperpigmented macules along the lines of Blaschko.

Lesions are mainly distributed on the trunk and extremities. It spares palms, sole and mucosae. The usual age of the onset is within the first few weeks of life and continues to progress for a year or two before stabilization. Histopathology reveals basal pigmentation.

Congenital melanocytic nevus

Congenital melanocytic nevi affect approximately 1% of newborn. It forms between 5 and 24 weeks of gestation and present at birth or become apparent within the 1st year of life42. The nevi can be round or oval with smooth, well- defined borders and the surface texture can be papular, rugose, verrucous or cerebriform. Although initially the nevus may be light in color, flat and hairless, it can become raised, more pigmented and acquire hypertrichosis. On the basis of their size, they are classified into

1) Small - less than 1.5 cm in greatest diameter

2) Medium - between 1.5 and 19.9 cm in greatest diameter

3) Large or giant congenital melanocytic nevi - 20 cm or more in greatest

diameter

Giant nevus often has “bathing trunks” and “glove stocking” distributions and can present with several smaller satellite lesions. The risk of development of melanoma ranges from 0% to 5% for small nevi, with one’s risk increasing to 5% to 10% for giant congenital melanocytic nevi43.

Nevus of Ota / nevus of Ito

Nevus of Ota and Ito are rare benign dermal melanocytoses. Nevus of Ota affects the skin along the distribution of ophthalmic and maxillary divisions of the trigeminal nerve44 where as nevus of Ito involves acromioclavicular region and the upper chest. Nevus of Ota occurs more commonly in Asians and blacks.

Nevus of Ota is more common in females. Both are typically unilateral but bilateral involvement has also been reported.

The extracutaneous lesions may be seen in eyelids, sclera, cornea, retina and other sites like tympanic membrane, nasal mucosa, pharynx, palate etc45, 46.

Pathology of both the conditions are identical, showing spindle shaped dendritic melanocytes in the upper and mid dermis47, 48.

Post inflammatory hyperpigmentation

These are poorly marginated, tan to dark brown lesions, of variable size and can be located at any site. It follows the sites of previous inflammatory conditions of skin and shows complete resolution.

HYPOPIGMENTED BIRTH MARKS

Nevus anemicus

It is an uncommon, localized, congenital vascular malformation which presents as hypopigmented macules and patches of varying size. It is due to localized vascular hyper sensitivity to the circulating catecholamines. It most commonly presents as a single patch on the trunk. Histopathological examination is absolutely normal. Thus nevus anemicus is a pharmacologic entity and not an anatomic one49, 50. On pressing the lesional border with the glass slide the demarcation between the nevus and normal skin disappears because the normal skin becomes blanched. The differential diagnoses include nevus depigmentosus,

Hansen’s disease, tinea versicolor, post inflammatory hypopigmentation,

33 pityriasis alba, tuberous sclerosis and vitiligo. No intervention is needed apart from parental reassurance.

Nevus depigmentosus

Nevus depigmentosus, called nevus achromicus is a rare congenital pigmentary disorder. It presents as a solitary, well-defined circumscribed area of depigmentation. The lesion is several centimeters in diameter, with irregular serrated borders that do not cross the midline. It is commonly seen on the trunk, neck, face and proximal part of the extremities but it can be found anywhere on the body. Diascopy test is negative, which is positive in nevus anemicus.

Clinically, three types have been designated namely

1) Localized

2) Segmental

3) Linear or Whorled

Among the above, localized is the most common variant. Extra cutaneous manifestations like seizures, mental retardation, hemi hypertrophy, and yellow hair may be seen in systematized variant.

The diagnostic criteria given by Coup help to differentiate it from other hypopigmented conditions51.

• Leukoderma presenting at birth or of early onset.

• No alteration in distribution of leukoderma throughout life.

• No alteration in texture or change in sensation in the affected site.

• Absence of hyperpigmented border.

Hypomelanotic macules of tuberous sclerosis

Hypomelanotic macules of tuberous sclerosis, is the earliest manifestation and it usually presents in 80% of affected individuals at birth or within the first two years of life52. It frequently presents on trunk or extremities. Though at times barely noticeable, these can be made prominent by Wood's light examination.

Three types of hypomelanotic macules are described, these are:

a) Polygonal or thumb print

b) Ash-leaf or lance ovate

c) Confetti like

It comes under the major diagnostic criteria of tuberous sclerosis complex.

It is considered significant if the number of lesions is more than three. It can also be seen in apparently normal newborn and therefore their presence alone is not indicative of tuberous sclerosis.

Piebaldism

Piebaldism is a rare autosomal dominant condition characterized by the congenital absence of melanocytes in affected areas of skin and hair. It is characterized by a congenital white forelock and multiple stable hypopigmented or depigmented macules and patches. Both sexes are equally affected and no race is spared. Depigmented macule is rectangular, rhomboid or irregular in shape and frequently has a symmetrical distribution. It has a predilection for anterior part of the body and mid-part of extremities. Typically, islands of hyperpigmentation are

35 present within and at the periphery of depigmented lesions. It is usually not associated with extracutaneous features. However mental retardation, deafness and aganglionic megacolon have been reported to be associated with it53.

Neonatal pityriasis versicolor

Colonization of skin by Malassezia begins in the first day of life, and it increases during the first few weeks. M. globosa is the most common colonizing species. Pityriasis versicolor is characterized by multiple, round to oval hypopigmented macules and patches or thin plaques that are covered with fine branny scales. The lesions are preferentially distributed over the seborrhoeic areas of the skin surface. In neonates, it often involves the face especially the paranasal area, in contrast to the rarity of facial involvement in adults. Risk factors associated with neonatal infection include genetic inheritance, gestational age, birth weight, duration of stay in an intensive care unit, presence of central venous catheters, elevated temperature and humidity of incubators, use of total parenteral nutrition, antibiotics and corticosteroids54. Simple KOH examination of scales helps is arriving at diagnosis and excluding it from other causes of hypopigmented lesions. It is usually treated with topical antifungal drugs. Systemic treatment with oral antifungals, such as fluconazole may be an option in extensive lesions and in those patients at risk of invasive disease.

Post-inflammatory hypopigmentation

These follow the sites of previous inflammation. It has variable shapes, sizes and poorly defined borders and can be seen anywhere on the body. With time it resolutes completely.

VASCULAR LESIONS

 Flat capillary malformations

i) Salmon patch

ii) Portwine stain

 Hemangioma

Flat capillary malformations

This is divided into two types, namely salmon patch and portwine stain.

Salmon patch also called nevus flammeus simplex is the most common vascular lesion of infancy. It is seen over the nape of neck in 40% (stork bite) and over the glabella in 20% (angel’s kiss) of infants. Portwine stain is seen in 0.5% of the babies.

Salmon patch is composed of ectatic dermal capillaries, which represents the persistence of fetal circulatory pattern. It appears as scarlet to pink totally blanchable macule or patch. Commonly involved sites are nape of neck, glabella, eyelids, lips and nose. Lesion over nape of neck may become inflamed and develop overlying dermatitis. It tends to fade with time and disappears completely occasionally remnants persist into adult life.

Portwine stain usually presents at birth and appears as deep red or purple macules over face or extremities. As the age advances it becomes raised darker nodular lesions. Usually unilateral, sometimes it can be extensive. Most common sites are face, neck, scalp, arm and legs. Facial lesion may be associated with soft tissue and bony hypertrophy.

Hemangioma

These are benign vascular tumors that appear as red or purple red macule or patch and are seen in 2% of the neonates. Most cases are sporadic and girls are more affected than boys. It starts as a faint telengiectatic patch or as a flat pink lesion or an area of pallor that rapidly becomes raised red papule or plaque.

Superficial, deep and mixed types are seen of which mixed type is more common.

Superficial type shows their maximum growth between 5.5 and 7.5 weeks of age. Deep hemangioma presents in later weeks of life and appear blue or purple with overlying normal skin. They continue to grow for longer period than the superficial type. Most of the infantile hemangiomas reach 80% of their final size by 12 weeks of age, irrespective of subtype or depth of involvement. The consistency is firm during proliferative phase and becomes softer during the involution stage. Abortive infantile hemangioma is a minor variant which shows little proliferation and remains as a patch of telengiectatic vessels.

Based on morphology it is classified into the following types

1) Superficial

2) Deep

3) Mixed

4) Reticular abortive

They can exist in different patterns like focal, multifocal, segmental and indeterminate.

Clinical variants

1) Segmental infantile hemangioma

2) Multifocal cutaneous infantile hemangioma with & without extracutaneous

involvement

3) Hepatic hemangioma

The median age of complete involution is 3 years. Therefore surgical intervention may be best considered after this age, as further spontaneous improvement and aesthetic benefits are unlikely after this period.

Permanent changes like telengiactases, atrophy, residual mass in the form of fibrofatty tissue may remain in up to 69% of untreated cases. Atrophic scars may undergo spontaneous ulceration.

Complications like bacterial infection, Kasabach Merritt syndrome, ulceration, bleeding and congestive cardiac failure may occur. With periocular

39 hemangioma functional impairment like astigmatism, visual axis obstruction and strabismus may develop. Finally disfigurement of face, lips and nose can also be seen when lesions are located on these regions particularly with a dermal component.

Prognosis is excellent for small infantile hemangiomas and good for hemangiomas causing functional or aesthetic impairment if treatment is started at correct time. Diagnosis is mostly clinical, but occasionally ultrasound may be needed to differentiate it from other soft tissue tumors or vascular malformations.

Treatment depends on location, morphology, stage of evolution and its impact on function. Serial photographs may help in assessing the size of the lesion over time.

Active non-intervention and parental reassurance is appropriate for lesions with no risk of disfigurement, impairment of function or ulceration. Various treatment options that can be tried are intralesional steroids, systemic steroids, topical 1% propranolol, 0.5 % timolol maleate, pulsed dye laser, surgery and embolization.

BLISTERING DISORDERS

Epidermolysis bullosa

It comprises a group of uncommon genetically determined heterogenous mechanobullous skin fragility disorders, which are characterized by blistering of the skin and mucosa, in response to trivial trauma. This complex is mainly

40 classified into EB simplex (EBS), junctional EB (JEB), and dystrophic EB (DEB).

Now kindler syndrome is added as fourth type to the existing classification.

Major forms of epidermolysis Level of cleavage bullosa EB simplex Intraepidermal Junctional EB Intralamina lucida Dystrophic EB Sublamina densa Kindler syndrome Mixed

Epidermolysis bullosa simplex

It is the most common form of EB. It is sub-classified into suprabasal EBS and basal EBS. It manifest as more than twelve distinct clinical phenotypes. It is autosomal dominantly inherited. Blister presents at birth and has predilection for hand, feet, elbow, knees and leg. Rarely nails become dystrophic and may be shed. As age advances the propensity of blisters decreases and long term prognosis is good.

Junctional epidermolysis bullosa

It is categorized into Generalized and localized forms. Generalized severe junctional EB is the most severe form of junctional EB. Blistering and erosions are present at or soon after birth and become rapidly generalized. Erosions are often very slow to heal with the resultant atrophic scarring. Milia are not generally seen, but they may develop if erosions get secondarily infected. Involvement of oral and pharyngeal mucosa is common and can be severe. Most infants die early 41 in the infancy period due to overwhelming infections or from failure to thrive.

Those surviving will often develop distinctive lesions characterized by non‐ healing, crusted erosions containing exuberant granulation tissue around the nose, mouth, neck, trunk, buttocks and rarely the upper respiratory tract.

Dystrophic epidermolysis bullosa

It can be dominant or recessive Dystrophic EB. Recessive type is the most incapacitating form. Clinically, it is characterized by skin and mucosal fragility, blistering, scarring, dystrophic nails and milia formation. The overall prognosis is generally poor.

Kindler syndrome

It resembles generalized or localized forms of dystrophic EB clinically, but skin biopsy classically shows a variable plane of cleavage. In most cases, the initial skin blistering lessens during childhood and signs of progressive poikiloderma supervene. The hands may also show evidence of pseudosyndactyly.

Chronic colitis may complicate some cases of Kindler syndrome.

Neonatal pemphigus vulgaris

Infants born to mother with pemphigus vulgaris develop transient flaccid cutaneous and or mucosal blisters and erosions. It is due to transplacental transmission of IgG autoantibodies from the mother’s circulation to the fetus. No specific treatment is needed as the lesions resolve spontaneously within about 2-3

42 weeks after delivery. It never persists beyond the neonatal period. No new lesions appear after birth and it does not have long-term clinical significance.

Transplacental pemphigoid gestationis

Cutaneous lesions developed in about 10% of infants born to females with herpes gestationis. The risk of transplacental transfer of autoantibodies is higher in preterm neonates. Lesions present as non-specific erythematous, urticarial papules or blister with erosion. Prognosis is favourable, and the lesions regress spontaneously without scarring.

Bullous congenital ichthyosiform erythroderma

It is also termed as epidermolytic hyperkeratosis. This is a rare autosomal dominant keratinizing disorder which affects both sexes equally. It is characterised by onset at birth with generalised erythroderma, desquamation and superficial fragile blisters. In the first weeks of life the skin acquires typical hyperkeratosis with flexural accentuation. The scales are small, dark, thick verrucous and assume a columnar configuration. Adnexa are spared generally and there is no visceral involvement. Recurrent bulla may develop and it may get secondarily infected. Palmoplantar keratoderma may be seen in severe cases.

Treatment includes antibiotics for secondary bacterial infection, emollients, keratolytics and retinoids. Genetic counselling should be provided.

Incontinentia Pigmenti

It is also called as Bloch-Sulzberger syndrome, is a rare X-linked dominant inherited disorder55, 56. Almost all cases are among females as the condition is lethal in males. It is characterized by four morphologic stages namely vesicular, verrucous, hyperpigmented, and atrophic hypopigmented stages. The condition results from the mutation in NEMO gene. Usually, the diagnosis is made clinically on the basis of history of sequential cutaneous changes and associated features. They may have varying degrees of eye, dental, skeletal and neurological involvement. There may be peripheral eosinophilia during the vesicular phase.

The following diagnostic criteria is proposed by Landy and Donnai in 1993

Diagnostic criteria in the absence of family history

Major criteria

. Typical neonatal vesicular rash

. Typical blaschkoid hyperpigmentation

. Linear, atrophic, hairless lesions.

Minor criteria

. Dental involvement

. Alopecia

. Wooly hair, abnormal nails

. Retinal diseases

Diagnostic criteria in the presence of family history

. Suggestive history or clinical evidence of typical rash

. Cutaneous manifestations of incontinentia pigmenti

. Dental abnormalities

. Wooly hair

. Retinal disorders

. Multiple abortions of male fetuses

In the absence of family history, atleast one major and minor criteria is required for the diagnosis. But in the scenario of positive family history, presence of any criteria strongly supports the diagnosis of incontinentia pigmenti.

Symptomatic treatment can be given according to the stages of lesion. No specific treatment is available for it. Routine dental and ophthalmologic follow-up is essential to prevent the visual morbidity. Neurological consultation is done only if neurologic symptoms are present. It can be associated with malignancies such as acute myelogenic leukemia, Wilm’s tumor and retinoblastoma. Prognosis varies depending on the degree of ocular, dental and central nervous system involvement.

MISCELLANEOUS CONDITIONS

Skin complications in the neonatal intensive care unit

Complication of phototherapy

Phototherapy for neonatal jaundice may produce tanning, transient rash, burns and bronze baby syndrome. It also precipitates congenital erythropoietic porphyria. Thus it is contraindicated in newborn with family history of porphyria.

Fetal scalp electrodes

These may cause scalp lacerations at the site of insertion. This is especially more common in preterm neonates as the scalp tissue is more fragile in those babies. The risk of neonatal sepsis is also increased57.

Umbilical artery catheterization

It increases the risk of bacterial and fungal infections and also of thrombotic and embolic phenomenon of large vessels like aorta.

Calcinosis cutis

Heel stick puncture is the most common cause of calcinosis in neonates. It presents clinically as white papule or nodule at prick site and heals spontaneously.

It can also occur over lead placement for EEG and ECG due to the use of calcium chloride containing electrode paste58.

Chemical burns

Isopropyl alcohol applied to skin as a disinfectant can cause 2nd and 3rd degree burns.

Sclerema neonatorum

It is a very rare condition presenting with generalized hardening of the subcutaneous tissue. It is a form of panniculitis usually affecting the preterm neonates. It is a nonspecific sign of grave illness. It develops mostly in the 1st 1-2 weeks of life but may also occur in the immediate postpartum and later weeks of life. The skin is bound to underlying subcutaneous tissue, even muscle and bones, therefore the skin cannot be picked up. The process starts on the buttocks, thighs or calves and rapidly extends to involve other parts of the body. Palms, soles and genitalia are usually spared.

Due to hardening movement, feeding and respiration are restricted. Skin is hard, cold to touch and yellowish white in colour with purplish mottling.

Prognosis is usually poor, in spite of aggressive interventions. Treatment of underlying condition is the key to survive. Systemic steroids, repeated exchange transfusion and intravenous immunoglobulins may substantially reduce mortality in some cases59.

Gray baby syndrome

It is a fatal syndrome due to the toxicity of antibiotic, chloramphenicol. It is most common in preterm neonates because of immaturity of liver and kidney.

Affected neonates develop irregular respiration, anemia, cyanosis, pallor, bleeding, organ failure, hypothermia, vasomotor collapse and even death60.

Other iatrogenic complications

1) Miliaria resulting from use of radiant warmers

2) Zinc deficiency in preterm neonates receiving long-term parenteral

nutrition

3) Scarring alopecia of the occipital scalp can also occur following

extracorporeal membrane oxygenation

Skin care of newborn babies

. Prevention of physical injury

. Maintaining thermoregulation

. Minimizing infections

. Lessening insensible water loss

Aim & objectives

AIM AND OBJECTIVES OF THE STUDY

1. To assess the prevalence of various dermatoses in the preterm neonates.

2. To determine the association between birth weight, gestational age, mode

of delivery, consanguinity and dermatoses.

3. To determine the systemic associations.

4. To identify any unusual cutaneous changes in the study group.

Materials & Methods

MATERIALS AND METHODS

Study design:

Cross sectional study

Study Centre

Neonatology Unit,

Institute of Obstetrics and Gynaecology (IOG),

Madras Medical College &

Rajiv Gandhi Government General Hospital, Chennai-3.

Study Period:

One year from June 2017 to May 2018.

Sample Size:

One hundred preterm neonates with cutaneous changes.

Inclusion criteria:

Preterm neonates with cutaneous changes born after 28 weeks and before

37completed weeks of gestational age during the study period.

Exclusion criteria:

1) Preterm neonates without cutaneous changes.

2) Term and post term neonates.

3) Parents not willing for the study.

One hundred preterm neonates with cutaneous changes were randomly selected for the present study among the babies born in maternity hospital,

Institute of obstetrics and gynaecology, Egmore, Madras Medical College,

Chennai for a period of 1 year from June 2017 to May 2018.

Preliminary information about neonate like gestational age, sex, birth weight, consanguinity, mode of delivery, natal history and postnatal care was elicited.

Regarding maternal history their age, parity, history of any Infection, radiation exposure, drug intake, comorbidities like diabetes mellitus, hypertension, connective tissue disorder etc., antenatal procedure, VCTC and

VDRL status during their antenatal period was taken.

General physical examination, systemic examination, complete dermatological examination including scalp, hair, nails, palms and soles, genitalia and mucosa of preterm neonates was done to record both the physiological and pathological conditions.

Simple non-invasive investigations like KOH mount for candida infection,

Tzanck smear, gram stain, dark field microscopy and pus culture were done in needed cases to confirm the dermatological diagnosis.

Blood investigations like full blood count, liver function test, imaging studies and other investigations was done in selected cases depending on the clinical diagnosis to confirm it and to rule out any systemic involvement.

STATISTICAL ANALYSIS:

The collected data were analysed with IBM.SPSS statistics software 23.0

Version. To describe about the data descriptive statistics frequency analysis, percentage analysis were used for categorical variables and the mean & S.D were used for continuous variables. To find the significance in categorical data Chi-

Square test was used similarly if the expected cell frequency is less than 5 in 2×2 tables then the Fisher's Exact was used. In both the above statistical tools the probability value .05 is considered as significant level.

ETHICAL ISSUES:

Neonates’ parents were made aware about the nature and purpose of the study. It was also informed to all the parents that all data provided by them will be kept confidential and will be used only for the study purpose. Willingness and signature were taken on a previously designed consent form. Written consents were obtained from all the parents who participated in the study before data are collected. Detailed description of the study and the aspects of patient confidentiality are explained to them and voluntary participation is sought.

Institutional ethics committee of Madras medical college reviewed the study proposal for ethical consideration and approval of the committee was obtained prior to the study.

Observations & Results

OBSERVATION AND RESULTS

TABLE 4: INCIDENCE OF VARIOUS DERMATOSES OBSERVED IN

THE STUDY GROUP

No. of babies Sl no Dermatoses Percentage (%) (n) 1 Milia 77 77 2 Epstein pearl 66 66 3 Mongolion spot 63 63 4 Physiological jaundice 40 40 5 M. crystallina 33 33 6 Lanugo hair 32 32 7 Skin peeling 14 14 8 Erythema toxicum neonatorum 10 10 9 Congenital anomalies 5 5 10 Ichthyosis vulgaris 4 4 11 Diaper dermatitis 3 3 12 Cutis marmorata 2 2 13 Miniature puberty 2 2 14 Cong. Melanocytic nevi 2 2 15 Collodion baby 1 1 16 Hemangioma 1 1 17 CALM 1 1 18 Aplasia cutis congenita 1 1 19 Contusion 1 1

DERMATOSES

0 Milia CALM Lanugo contusion Skin Skin peeling M crystallina M Epsteinpearl Hemangioma Colodion baby Mongolianspot CutisMarmorata Diaper dermatitis Diaper Ichthyosisvulgaris Erythema Erythema toxicum Miniature Miniature puberty Congenitalanomalies Physiologicaljaundice Cong Melanocytic neviMelanocyticCong Aplasia cutis congenita Aplasiacutis Incidence of various dermatoses

The above graph shows incidence of various dermatoses observed in our study population in descending order.

Table 5: Maternal age

The age of the mother ranges from 18 to 37 years with the mean age of

25.5 years.

S No Variables (age in years) Frequency N (%)

15-24 38 (38%)

1 Mother age 25-34 58 (58%)

35-44 4 (4%)

70 58% 60

50 38% 40

10 4%

0 15-24 25-34 35-44 maternal age (years)

Maximum number of mothers was in the age group of 25 to 34 years and only 4% in the age group of 35 to 44 years. There was no significant association between maternal age and the various dermatoses observed in the neonates.

Table 6: Maternal illness

S Variables Frequency N (%) No Present 26 (26%) 1 Maternal illness Absent 74 (74%)

Maternal illness

Present 26%

Absent 74%

Of the 100 mothers 26 % had associated comorbidities during their antenatal period. Hypertensive disorder (14%) was the most common illness seen followed by hypothyroidism 5%, anemia 3%, diabetes mellitus 2%, SLE and

RHD each 1%. We did not find any statistical association between maternal illness and neonatal dermatoses both physiological and pathological.

CAUSE OF PRETERM DELIVERY

60 51%

50 25%

40 15% 08% 30 01%

0 Fetal Distress Unknown PPROM Oligo Abruption Hydramnios Cause Of preterm Delivery

We found that there was no significant association between various causes of preterm delivery and different dermatoses (both physiological and pathological) observed in our study.

Table 7: Physiological and pathological dermatoses

S Variables Frequency N (%) No Physiological 79 (79%)

1 Conditions Pathological 15 (15%)

Both 6 (6%)

Percentage of dermatoses

Both Pathological 6% 15%

Physiological 79%

PHYSIOLOGICAL AND TRANSIENT CONDITIONS

Table 8: Milia

Milia was seen in 77 babies of the 100 examined.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 2 to C NC Primi Multi CS LN M F ≤ 2 >2.5 wks wks 2.5

No of 9 68 39 38 51 26 42 35 31 46 56 18 3 babies

Percentage 11.7 88.3 50.6 49.4 66.2 33.8 54.5 45.5 40.3 59.7 72.7 23.4 3.9

(C-consanguinous, CS-caesarean section, M- male, F- female, NC-non

consanguinous, LN-labour naturalis)

This the most common dermatoses encountered in our study. 77% of the

babies had milia. Out of 77 neonates with milia, 68 (88.3%) were born to non

consanguinous parents. 59.7 % were female and 40.3% of the babies were females

and males respectively.

Table 9: Epstein pearl

This condition was seen in 66% of the babies examined.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 2 to C NC Primi Multi CS LN M F ≤ 2 >2.5 wks wks 2.5

No of 5 61 36 30 42 24 43 23 20 46 49 15 2 babies

Percentage 7.6 92.4 54.5 45.5 63.6 36.4 65.2 34.8 30.3 69.7 74.2 22.7 3.1

It was the second most common condition observed during the study

period. It is more common in those babies born out of non consanguinous

marriage 61 (92.4%). 69.7% of the Epstein pearl was seen in female babies.

74.2% of the babies with this condition fall in the birth weight category of less

than 2 kg.

Table 10: Mongolian spot

Mongolian spot was seen in 63 (63%) babies of the total 100 screened.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 2 to C NC Primi Multi CS LN M F ≤ 2 >2.5 wks wks 2.5

No of 8 55 30 33 44 19 35 28 24 39 48 14 1 babies

Percentage 12.7 87.3 47.6 52.4 69.8 30.2 55.6 44.4 38.1 61.9 76.2 22.2 1.6

The next common dermatosis noted in the study was Mongolion spot. It

was seen more commonly on the lumbosacral area. 55(87.3%) babies had the

Mongolion spot in the lumbosacral region and 8(12.6%) babies had lesions in the

sacral area. It was more common in female babies and those weighing less than 2

kg birth weight.

Table 11: Physiological jaundice

Icterus was seen in 40 (40%) neonates.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 ≤ 2 to C NC Primi Multi CS LN M F >2.5 wks wks 2 2.5

No of 2 38 22 18 26 14 29 11 17 23 34 5 1 babies

Percentage 5 95 55 45 65 35 72.5 27.5 42.5 57.5 85 12.5 2.5

Icterus observed in all babies was physiological in nature. It developed on

≥2 days of life and resolved within 1- 2 weeks of life when followed up. It was

more common in babies with birth weight of less than 2 kg (85%) and neonates

born less than 34 weeks of gestational age (72.5%).

Table 12: Miliaria crystallina

Miliaria crystallina occurred in 33% of the neonates.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 2 to C NC Primi Multi CS LN M F ≤ 2 >2.5 wks wks 2.5

No of 3 30 21 12 23 10 20 13 12 21 23 8 2 babies

Percentage 9.1 90.9 63.6 36.4 69.7 30.3 60.6 39.4 36.4 63.6 69.7 24.2 6.1

Of the 33 neonates with Miliaria crystallina, 21 were females and 12 were

males. It occurred more commonly in neonates with less than or equal to 2 kgs of

birth weight. It was more commonly seen over the scalp, forehead and neck

region.

Table 13: Lanugo hair

Lanugo hair occurred in 32% of the preterm babies.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 2 to C NC Primi Multi CS LN M F ≤ 2 >2.5 wks wks 2.5

No of 3 29 17 15 22 10 29 3 17 15 26 5 1 babies

Percentage 9.4 90.6 53.1 46.9 68.8 31.2 90.6 9.4 53.1 46.9 81.2 15.6 3.1

29 out of 32 babies with lanugo were born out of non consanguinous

marriage. Higher percentage was seen in babies with ≤ 34 weeks of gestational

age (90.6%) and birth weight of less than or equal to 2 kg (81.2%).

Table 14: Skin peeling

Physiological peeling of the skin was noted in 14% of the preterm babies.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

≤ 34 > 34 2 to C NC Primi Multi CS LN M F ≤ 2 >2.5 wks wks 2.5

No of 0 14 9 5 10 4 8 6 6 8 4 9 1 babies

Percentage 0 100 64.3 35.7 71.4 28.6 57.1 42.9 42.9 57.1 28.6 64.3 7.1

Male and female babies with this condition were 42.9% and 57.1%

respectively. 9/14 (64.3%) neonates had birth weight of 2- 2.5 kg. Most of the

neonates had peeling limited to extremities.

Table 15: Erythema toxicum neonatorum (ETN)

Its incidence was 10% among 100 newborn.

Mode Gestational Birth weight Consanguinity Parity of Sex Age (kg) delivery

2 ≤ 34 > 34 ≤ C NC Primi Multi CS LN M F to >2.5 wks wks 2 2.5

No of 2 8 7 3 7 3 1 9 3 7 4 6 0 babies

Percentage 20 80 70 30 70 30 10 90 30 70 40 60 0

Of the total babies screened, only 10 (10%) neonates had erythema

toxicum neonatorum. 7 out of 10 babies were born to primigravida. 90% of the

babies with ETN were born after 34 weeks of gestation. This value shows that

ETN was more common in babies born towards the term period. All 10 babies had

birth weight of less than 2.5 kg.

We observed congenital anomalies in 5% of the study population.

Incidence of ichthyosis vulgaris was 4%, diaper dermatitis was 3% and miniature

puberty was 2%.

Two cases had congenital melanocytic nevi and cutis marmorata. We

encountered a single case of collodion baby, hemangioma, calf-au-lait macule,

aplasia cutis congenita and contusion during the study period.

Table 16: Combination of various physiological dermatoses

Sl Combination of physiological dermatoses Frequency N (%) No

0 3 (3%)

1 3 (3%)

2 17 (17%)

3 34 (34%)

1 Dermatoses 4 25 (25%)

5 13 (13%)

6 4 (4%)

7 1 (1%)

8 0 (0%)

Combination of physiological dermatoses 40% 34% 35% 30% 25% 25% 20% 17% 13%

Percentage 15% 10% 4% 5% 3% 3% 1% 0% 0% 0 1 2 3 4 5 6 7 8 Number of Dermatological Conditions

34% of the neonates showed combination of 3 physiological conditions and

25% of showed 4 conditions. There was no statistical significance between various combinations of physiological dermatoses except physiological jaundice and lanugo hair (p value-0.002).

Table 17: Physiological Jaundice Vs Lanugo hair

Lanugo hair Variables Present Absent

Present 20 (62.5%) 20 (50%) Physiological Jaundice Absent 12 (37.5%) 48 (80%)

Chi- square value – 9.926 p value 0.002 (statistically significant)

Physiological Jaundice Vs Lanugo 70% 62.50% 60% 50.00% 50.00% 50%

40% 37.50%

30% Percentage 20%

10%

0% Present Absent

Physiological jaundice Present Absent

Consanguinity

89%

Parity

55%

45%

Mode of delivery

65%

35%

Gestational age

57%

43%

Baby sex

61%

Birth weight

60 71%

20 25% 10 04%

0 Upto 2 kg 2 to 2.5 Kg More than 2.5 Kg Birth weight

Incidence of milia

77%

23%

Incidence of epstein pearl

66%

34%

Incidence of mongolion spot

63% 37%

Incidence of physiological jaundice

60%

40%

Incidence of miliaria crystallina

67%

33%

Incidence of lanugo hair

68%

32%

Incidence of physiological desquamation

86%

14%

Incidence of erythema toxicum neonatorum

90%

10%

Clinical Images

CLINICAL IMAGES

MILIA

EPSTEIN PEARL

MONGOLIAN SPOT

MILIARIA CRYSTALLINA

LANUGO HAIR

PHYSIOLOGICAL PEELING OF SKIN

ERYTHEMA TOXICUM NEONATORUM

CUTIS MARMORATA

EXSTROPHY OF BLADDER

CLEFT LIP AND PALATE VENTRAL CHORDEE

ICHTHYOSIS VULGARIS

CONGENITAL MELANOCYTIC NEVI

CAFE-AU-LAIT MACULE

HEMANGIOMA

COLLODION BABY

Discussion

DISCUSSION

This study was carried out as a clinico-epidemiological survey of dermatoses in preterm neonates from June 2017 to May 2018. Preterm neonates delivered in the Neonatology Unit, Institute of Obstetrics and Gynaecology (IOG),

Madras Medical College & Rajiv Gandhi Government General Hospital, was examined for cutaneous lesions. The sample size was 100.

Minimum gestational age of the preterm neonate was 29 weeks and maximum gestational age 35 weeks and 5 days with the mean age was 34 weeks.

Female to male sex ratio was 1.56.

Of the 100 neonates, 89% were born out of non-consanguinous marriage and only 11% of the babies were born to consanguinous parents. 55% of the babies were born to primigravida and 45% to multigravida mother. Regarding mode of delivery 65% of the studied population were delivered by cesarean section and 35% by normal delivery. 57% of the babies were born on or before 34 completed weeks and the rest 43% of the neonates born after it. Most of the neonates (71%) had birth weight of less than 2 kg, 25% had birth weight between

2 and 2.5 kg and only 4% had more than 2.5 kg birth weight.

In this study 79% of the neonates had physiological changes and 15% had pathological conditions and 6% had both physiological and pathological changes together.

The main physiological changes observed in our study were milia, epstein pearl, mongolian spot, physiological jaundice, miliaria crystallina, lanugo hair, superficial desquamation, erythema toxicum neonatorum and cutis marmorata.

Pathological conditions were congenital anomalies, ichthyosis vulgaris, collodion baby, cafe au-lait macule, congenital melanocytic nevi, contusion, hemangioma, diaper dermatitis and aplasia cutis congenita.

Among the various dermatological manifestations, the most common condition observed was milia 77 (77%). The frequency of this condition had varied considerably in different studies, 5.3% in a study by Shehab et al and

94.8% in a study conducted by Mishra et al61, 62. It was more frequent in female sex (59.7%), newborn born out of non-consanguinous marriage (88.3%) and those delivered by cesarean section. Neonates with birth weight of less than 2 kgs had more incidence of milia 72.7%. It was comparable in babies born to primi and multigravida. In majority of the neonates, milia occurred over nose, cheeks and chin.

Epstein pearl was the second most common condition observed in 66% and was significantly more (p value 0.013) in female sex and neonates born less than

34 weeks of gestation (p value 0.022). Its incidence was comparable with the study conducted by Nobby et al, that they reported a prevalence of 57.6%63. Most of our patients had Epstein pearl at the junction of hard and soft palate.

In this study mongolian spot was seen in 63% of the newborn. The frequency of mongolian spot is almost comparable with other Indian studies64, 65,

66, 67. Mongolian spot was seen more in female sex and in the primigravida.

Mongolian spot has been shown to be good example of inter-racial differences. Its prevalence has been as high as 80 to 90% in Asians67, and as low as 3 to 10% in

Caucasians68.

Physiological icterus was present in 40% of the population. It was more common in babies with birth weight less than 2 kg (85%) and neonates born less than 34 weeks of gestation (72.5%) and the p value was 0.041 and 0.011 respectively. There was no significant difference in sex distribution, parity, consanguinity and mode of delivery. From this observation, we can conclude that neonates with less gestational age were more prone to icterus because of the immature red blood cells and liver.

The frequency of miliaria crystallina was 33%. Earlier studies showed this condition varying from 1.8%69 to 20%70. It was more common in female sex, primigravida and those with birth weight of less than or equal to 2 kg.

Lanugo hair was seen in 32% of the examined neonates. Our finding was in contrast to that of Shivakumar et al71 and Jain et al72, who found that the incidence of lanugo was 72.4% and 82.7% respectively. It was more common in male sex whereas in Jain et al72 study it was more common in female babies. It was noticed more in neonates born by caesarean section, with gestational age less than 34 weeks and with the birth weight of less than 2 kgs. Statistically significant

86 association was found between lanugo and gestational age (p value 0.0005) and in male babies with the p value of 0.047. Most of the neonates showed lanugo over the face, shoulder and the back.

Physiological peeling of skin was noted in 14% of the babies. This condition constituted 5.4%69 to 33.3%73 in other studies. All the cases were seen in non consanguinous marriage. It was observed more common in females and babies born by cesarean delivery but it was more in males in Naveen et al study73.

This difference in sex distribution may be due to more number of female babies witnessed in this study. It was seen mostly over the distal part of the extremities.

Of the 14 neonates, 64.3% babies had birth weight of 2- 2.5 kg and 64.3% were born to primigravida. Association between birth weight of 2-2.5 kg and skin peeling was statistically significant (P value 0.001).

The number of cases of erythema toxicum neonatorum was 10 (10%). In other studies the incidence of this condition ranged from 0%73 to 23%72. It was significantly higher (p value 0.002) in neonates born after than 34 weeks of gestation and in babies with birth weight of 2 to 2.5 kg (p value 0.025). 90%

(9/10) of the babies with erythema toxicum were born after 34 week of gestational age. It was found more in neonates delivered by cesarean section as in a study by

Jain et al72. In most of the studied babies the lesion started after 4th day of life and disappeared within one to two days in 40% and within 3-5 days in the rest.

Congenital anomalies were observed in 5% of the study population. They were partial congenital talipes equinovarus, cleft lip and palate, preauricular tag, exstrophy of the bladder with urogenital anomaly and ventral chordee. All were born out of non-consanguinous marriage. There was no history of exposure to any drug, radiation or comorbidity in the antenatal period except maternal history of type 2 diabetes mellitus in neonate born with preauricular tag.

The incidence of ichthyosis observed in our study was 4%. All the cases were of ichthyosis vulgaris type. Both male and female sexes were equally affected. 75% (3/ 4) of the cases were born to consanguinous parents. All babies had gestational age more than more than 33 weeks. All the neonates were born to primigravida. Positive family was present in one case only.

Diaper dermatitis was seen in 3% of the neonates which was comparable to

1.6% in a study by Jain et al72.

Congenital melanocytic nevus was noted in 2% of babies screened.one was noted on the lower torso on right side and another on inner aspect of right knee.

Sex distribution was equal in our study. Both the lesions measured less than 1 cm

(6 x 3 mm, 3 x 3 mm) and so the risk of transformation into malignant melanoma was less than 0.1%. No history of similar lesion in the sibling and his parents.

Miniature puberty was diagnosed if they had genital hyperpigmentation, breast enlargement, witch’s milk, pigmented linea alba and vaginal discharge or frank vaginal bleeding in female babies. 2 % of our study population had

88 miniature puberty. In other studies the incidence ranged from 5.6 %78 to 61.5%72.

Both the cases were seen in female babies, primigravida and both had whitish mucous vaginal discharge. It subsided within 7 to 15 days after delivery.

We observed cutis marmorata in 2% neonates which is in divergence to

Jain et al72 who reported that cutis marmorata occurs in 23% of the preterm cases.

Cafe-au-lait macule was seen in 1%, the concurrence of these macules in previous study was 1.6%65. This macule presents on the posterior aspect of thigh, in a female baby born by natural labour. The size of the macule was around 0.3 x

0.4 cm. Neonate also had associated milia, Mongolian spot and Epstein pearl.

There was no history of similar illness or neurofibroma in the other family members.

One baby had hemangioma over the right upper eyelid of size 4 x 4 mm.

The mother was diagnosed with pregnancy induced hypertension during the 7th month and started on oral nifidepine. But till date no causal association between oral nifidepine and the occurrence of hemangioma was reported in the literature.

A chance finding in our study was that of a case of collodion baby (1%). It is comparable to 3% of incidence in shah et al study70. It was a female baby, born out of 2nd degree consanguinity but there was no history of similar illness in any of the family members.

We encountered one case of aplasia cutis congenita (1%) during our study period. The lesion was observed over the vertex region of scalp. There were no associated anomalies and the defect was limited to the skin. No history of maternal exposure to antithyroid drugs during the antenatal period and the baby was delivered by cesarean section. This was in concordance with the incidence of

2.3%, in a study by Shehab et al61.

One neonate had contusion in left forearm which was assumed to be the result of trauma during delivery. Coagulation profile of the baby was normal and there was no history of any anticoagulant drug intake in the mother during the antenatal period. So the ecchymosis was mostly attributed to birth trauma.

The differences in the observation in our study when comparing other studies may be due to inclusion of preterm neonates alone, more number of female babies, high number of cesarean delivery came across in this study and others may be due to racial and environmental factors.

Summary

SUMMARY

The present study was aimed to assess the prevalence of various dermatoses in the preterm neonates and to determine the association between birth weight, gestational age, modes of delivery, consanguinity and dermatoses and to find any systemic associations.

The study included 100 preterm neonates with cutaneous changes. They were examined to document information regarding gestational age, sex, birth weight, consanguinity, maternal history, antenatal, natal and post natal history and mode of delivery. Baby and mother were examined to record both physiological and pathological conditions.

In this study, prevalence of physiological cutaneous changes (79%) was much higher than pathological skin changes (15%) emphasizing the fact that in most cases we need to do no intervention but to know about the particular entity and its natural sequence of events.

Milia was the most common physiological condition (77%) among the study group.

Epstein pearl (66%), mongolian spot (63%), physiological jaundice (40%), miliaria crystallina (33%), lanugo hair (32%), superficial desquamation (14%) and erythema toxicum (10%) were other common physiological skin conditions encountered in the study population, in that order.

Regarding associations of various dermatoses, statistically significant association between gestational age (≤ 34 weeks) and physiological jaundice, lanugo hair, and epstein pearl was found. Erythema toxicum was seen more common in babies with more than 34 weeks of age.

Epstein pearl and lanugo were more common in female and males babies respectively.

Physiological desquamation and erythema toxicum were significantly more in neonate with birth weight between 2 and 2.5 kg, but physiological jaundice was more frequent in preterm with birth weight of ≤ 2kg.

No association was found between milia, mongolian spot, Miliaria crystallina and sex, gestational age, birth weight. No significant relationship was found between the mode of delivery, consanguinity, parity and any of the common dermatoses observed in our study.

LIMITATION OF THE STUDY

The sample size was small, hence further studies with a bigger sample size is needed to validate the findings of our study.

STRENGTH OF THE STUDY

As it was conducted in a tertiary care hospital, sample encompassed wide range of presentations.

Conclusion

CONCLUSION

From the results obtained from 100 subjects of this study, the following conclusions can be arrived at:

1. Physiological changes were more common than pathological conditions.

Milia was the most common dermatoses followed by Epstein pearl,

mongolian spot and other conditions.

2. Lanugo hair, physiological icterus and Epstein pearl were more frequent

in neonates with ≤ 34 weeks of gestational age.

3. Erythema toxicum neonatorum was more common in babies with birth

weight of 2-2.5 kg and with age >34 weeks. Thus erythema toxicum

neonatorum was more common in neonates born towards the term period.

4. No correlation was found between the mode of delivery, consanguinity,

parity and any of the common dermatoses.

Although the skin changes in neonatal period are common, the majority are benign and transient thus requires no treatment. We should be aware of these dermatoses and able to differentiate them from serious and life threatening conditions in order to avoid unnecessary diagnostic evaluation and treatment. The parents and family members need to be reassured about the self-limiting nature of these conditions.

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48) Mckee HP. Pathology of the skin with clinical correlations. ELSEVIER MOSBY.2005;12:1599-601. 49) Mountcastle EA, Diestelmeier MR, Lupton GP. Nevus anemicus. Journal of the American Academy of Dermatology. 1986 Apr 1;14(4):628-32. 50) Requena L, Sangueza OP. Cutaneous vascular anomalies. Part I. Hamartomas, malformations, and dilatation of preexisting vessels. Journal of the American Academy of Dermatology. 1997 Oct 1;37(4):523-49. 51) Coup RL. Unilateral systemic achromic naevus. Dermatologica 1976;136:19-35. 52) Fitzpatrick TB, Szabó G, Hori Y, Simone AA, Reed WB, Greenberg MH. White leaf-shaped macules: Earliest visible sign of tuberous sclerosis. Archives of dermatology. 1968 Jul 1;98(1):1-6. 53) Mahakrishnan A, Srinivasan MS. Piebaldism with Hirschsprung’s disease. Arch Dermatol 1980;116:1102. 54) Ahtonen P, Lehtonen OP, Kero P, Tunnela E, Havu V. Malassezia furfur colonization of neonates in an intensive care unit. Mycoses. 1990 Nov;33(11- 12):543-7. 55) Narendrqn V, Hoath SB. The skin. Martin RJ, Fanaroff AA, Walsh MC. Neonatal- Perinatal Medicine: Disease of the fetus and infant. 8th edition, Mosby. Philadelphia. 2006;2:1702. 56) Chang CH. Incontinentia pigmenti. http:// www.emedicine.com/neuro/topic 169.htm. 2007/ 04/19. 57) Kawakita T, Reddy UM, Landy HJ, Iqbal SN, Huang CC, Grantz KL. Neonatal complications associated with use of fetal scalp electrode: a retrospective study. BJOG: An International Journal of Obstetrics & Gynaecology. 2016 Oct 1;123(11):1797-803. 58) Sakmann S, DeSilva P. Neonatal heel-prick testing leading to dystrophic calcification. BMJ case reports. 2013;2013. 59) Kellum RE, Ray TL, Brown GR. Sclerema neonatorum: Report of case and analysis of subcutaneous and epidermal-dermal lipids by chromatographic methods. Archives of dermatology. 1968 Apr 1;97(4):372-80. 60) Krasinski K, Perkin R, Rutledge J. Gray baby syndrome revisited. Clinical pediatrics. 1982;21(9):571-2. 61) Shehab MM, Youssef DM, Khalil MM. Prevalence of cutaneous skin lesions in neonatal intensive care unit: A single center study. Journal of Clinical Neonatology. 2015 Jul 1;4(3):169. 62) Mishra PC, Mathur GP, Mathur S, Singh YD, Sharma D, Gupta AK. Normal anatomic variants in the newborn. Indian pediatrics. 1985 Sep;22(9):649-52. 63) Nobby B, Chakrabrty N. Cutaneous manifestations in the new born. Indian Journal of Dermatology, Venereology, and Leprology. 1992 Mar 1;58(2):69. 64) Nanda A, Kaur S, Bhakoo ON, Dhall K. Survey of cutaneous lesions in Indian newborns. Pediatric dermatology. 1989 Mar;6(1):39-42. 65) Kulkarni ML, Singh R. Normal variants of skin in neonates. Indian Journal of Dermatology, Venereology, and Leprology. 1996 Mar 1;62(2):83. 66) Dash K, Grover S, Radhakrishnan S, Vani M. Clinico epidemiological study of cutaneous manifestations in the neonate. Indian Journal of Dermatology, Venereology, and Leprology. 2000 Jan 1;66(1):26. 67) Hidano A, Purwoko R, Jitsukawa K. Statistical survey of skin changes in Japanese neonates. Pediatric dermatology. 1986 Feb;3(2):140-4. 68) Alper JC, Holmes LB. The incidence and significance of birthmarks in a cohort of 4,641 newborns. Pediatric dermatology. 1983 Jul;1(1):58-68. 69) Asha GS, Shilpa VK, Ramesh M, Revathi TN (2016) Clinical Study on Prevalence of Cutaneous Lesions in New Born Babies in India. J Clin Exp Dermatol Res 7:370. doi:10.4172/2155-9554.1000370 70) Shah S, Yaseen U, Gupta S. A clinical study of neonatal dermatosis. International Journal of Contemporary Pediatrics. 2017 Aug 23;4(5):1664-71. 71) Shivakumar S, Manjunathswamy BS, Metgud T, Doshi B. Cutaneous manifestations in neonates: A 1-year cross-sectional study in a tertiary care hospital. Indian Journal of Health Sciences and Biomedical Research (KLEU). 2018 May 1;11(2):125. 72) Jain N, Rathore BS, Agarwal AK, Bhardwaj A. Cutaneous lesions in neonates admitted in a tertiary setup neonatal intensive care unit. Indian Journal of Paediatric Dermatology. 2013 Sep 1;14(3):62. 73) Naveen KN, Bagalkote PS, Shetty SM, Dixit U. Cutaneous lesions in neonatal intensive care unit in a tertiary care center. Journal of Pakistan Association of Dermatology. 2018 Jul 11;27(2):124-30. 74) Sachdeva M, Kaur S, Nagpal M, Dewan SP. Cutaneous lesions in new born. Indian Journal of Dermatology, Venereology, and Leprology. 2002 Nov 1;68(6):334.

Annexures

ABBREVIATIONS

VCTC - Voluntary counselling and testing centre

VDRL - Venereal disease research laboratory

KOH - Potassium hydroxide examination

HIV - Human immunodeficiency virus

CALM - Cafe-au-lait macule

LWNH - Linear and whorled nevoid hypermelanosis

EBS - Epidermolysis bullosa simplex

JEB - Junctional epidermolysis bullosa

DEB - Dystrophic epidermolysis bullosa

MASTER CHART cause of baby age baby mom consan mode of birth Prenatal comp / physiological epstein miniature congenital sl no parity preterm milia M.crystallina mongolian ET lanugo skin peeling nevi ichthyosis others (weeks) sex age guinity delivery wt drug intake jaundice pearl puberty anomalies delivery 1 32+2 M p2 32 NC ECS 1.52 FD oligoH S S S S N N S N

2 32+3 M p1 27 NC LN 1.71 U eclampsia S N S N N N S N

3 33+4 F p1 21 NC ECS 1.44 oligo eclampsia S N N S S N N N cutis 4 32+2 F p3 33 NC ECS 1.23 FD Triplet, anemia N S S N S N S N marmorata 5 31 M p1 21 NC ECS 1.5 FD S S S S N N S N

6 36+1 M p1 22 3 ECS 2.2 PPROM N S S N S S N N Ichthyosis vulgaris

7 36+4 F p2 25 NC LN 1.69 U Anemia N S S N S S N N

8 35 F p1 20 NC ECS 2.42 oligo Hypothyroid N S S N S N N S S PIH,labetolol 9 30 M p1 24 NC ECS 2.09 FD S N S N S N S S 100mg bd 10 33+1 F p1 23 NC LN 2.6 U N N S N N N S N

11 36 F p1 24 NC ECS 2.32 FD N S S N S N N S

12 32+4 F p2 24 NC ECS 1.24 PPROM Hypothyroid N N S S S N S N

13 32+1 M p3 29 2 ECS 1.61 FD S S S N S N S N contusion

14 33+2 F p1 19 NC LN 2.12 U N S S N S N N S

15 33+3 M p3 27 NC ECS 1.73 FD N S S N S N N N

16 30+1 F p1 21 NC LN 1.29 PPROM S S S S N N S N

17 32 F p1 25 NC LN 1.32 U S N N S S N N N

18 36+3 M p2 30 NC LN 2.09 U oligoH N S S N S S N N

19 36 F p1 23 NC ECS 1.67 FD T.labetolol N N N N N N N N

20 33+6 F p2 26 NC ECS 1.67 abruption Hypothyroid N S S N S N N S

21 35 F p2 28 2 ECS 2.24 FD N N N N N N N N Collodion baby PIH,labetolol 22 34+6 F p2 29 NC ECS 1.75 FD N S S N S N N N 100mg od PIH,Mgso4,nifedip 23 34 F p1 21 NC LN 2.25 U N S N N N N S N hemangioma ine PIH.Mgso4, 24 33+3 F p1 18 NC ECS 1.75 FD N S S N N N S N labetolol,dexa 25 36+3 M p2 26 NC ECS 3.2 FD IDM,OligoH N N S N S N N N Preauricular tag

26 32+4 F p1 25 NC ECS 2.1 FD S S S S S N S S

27 35 M p1 20 3 ECS 1.71 FD oligoH N S S N S N N N

28 33+3 f p1 23 NC LN 1.93 U S S S N S N N S CALM cause of baby age baby mom consan mode of birth Prenatal comp / physiological epstein miniature congenital sl no parity preterm milia M.crystallina mongolian ET lanugo skin peeling nevi ichthyosis others (weeks) sex age guinity delivery wt drug intake jaundice pearl puberty anomalies delivery cong.M 29 33 M p2 22 NC LN 2.02 U N S S S N N N N nevi 30 33+3 F p1 24 NC LN 1.71 U N S S N N N N N

31 35 M p1 19 2 ECS 1.5 FD N N N S S N S N Ichthyosis vulgaris SLE-7 yrs,aza 32 36 F p2 27 NC ECS 2.63 oligo 100mg,HCQ,Pred N S N S N N N S 3od 33 34 M p3 34 NC ECS 1.9 PPROM labetolol, Dexa N S S N S N N S

34 33 M p2 24 3 LN 1.9 PPROM N N S N N N N N

35 34+5 M p2 26 NC ECS 1.8 FD N N S N N N N N

36 34 F p1 28 NC ECS 1.8 PPROM N S S N S N N N

37 34 F p1 21 NC LN 1.8 U N S S N S N N N

38 34 F p1 28 NC ECS 1.84 FD N S N S N N N N

39 30 M p2 24 NC ECS 1.6 FD N N S N S N S N Cleft lip, cleft 40 35+1 M p1 23 NC LN 2.37 FD N N S S N N N S palate 41 35 F p3 26 NC LN 1.56 FD Hypothyroid N S S N N N N N

42 34 F p1 31 NC ECS 1.6 FD Hypothyroid S S N N S N N N

43 34+5 F p3 28 NC LN 1.78 U N S S N S N N N

44 31+2 M p1 20 NC ECS 1.45 oligo N N N N S N S N

45 32+5 F p1 33 NC ECS 1.6 FD S S N S N N S N

46 30+4 F p2 35 NC ECS 1.91 FD S S S N S N S N

47 33 F p1 22 NC LN 2.1 FD N S S N N N N N

48 35+2 M p1 20 2 ECS 2.2 FD N N S S N N N N

49 32+2 F p1 24 NC LN 2 U S S S S N N S N

50 36 M p2 26 NC ECS 1.85 PPROM N S S N S N N S

51 35 F p1 25 NC ECS 1.32 FD S S S S S N N N S

52 34+1 F p2 29 NC LN 1.78 U S N S N S N N N

53 33+2 F p2 26 NC ECS 1.65 FD N S S N S N N N

54 34+3 M p1 18 NC ECS 1.94 oligo N N S N N N S N

55 33 F p1 27 NC ECS 1.57 FD S N S N S N N N

56 31 F p1 23 NC LN 1.6 PPROM S S N N S N S N

57 36+1 F p1 31 NC ECS 2.1 FD N N S S N S N N cause of baby age baby mom consan mode of birth Prenatal comp / physiological epstein miniature congenital sl no parity preterm milia M.crystallina mongolian ET lanugo skin peeling nevi ichthyosis others (weeks) sex age guinity delivery wt drug intake jaundice pearl puberty anomalies delivery Anemia,thromboc diaper 58 36+5 F p1 25 NC ECS 1.8 FD N S S N N S N N ytopenia dermatitis 59 33+4 F p1 25 NC ECS 1.3 FD N S S S N S N N Ichthyosis vulgaris

60 32+5 F p2 23 3 ECS 1.23 FD S S S S S N S N

61 34+6 M p1 26 NC LN 1.7 FD N N N N N N N N

62 31+4 F p2 27 NC LN 1.9 PPROM S S S N S N S N

63 34 F p1 25 NC LN 1.86 U N S N S S N N N

64 35+3 F p2 26 NC ECS 1.32 FD N S N S S N N N

65 36 F p1 36 NC ECS 2.23 FD N N S N N N N S aplasia cutis

66 33+2 M p3 33 NC ECS 1.87 oligo PIH S S S N S N S N

67 34+6 F p2 27 NC LN 1.32 U S N s N S N N N

68 33+1 M p1 23 NC LN 1.67 PPROM N S N N N N S N

69 32+4 M p1 26 NC ECS 1.41 FD S N S N S N S N

70 34 F p1 24 NC ECS 1.8 FD S S S N N N N N

71 35 M p2 26 NC LN 1.23 U S N S N S N S N

72 36+3 F p2 25 NC ECS 2.33 FD N N S S S S N N

73 34+5 M p1 25 NC ECS 1.75 FD PIH S N S N S N N N

74 36 F p3 29 NC LN 1.5 U N S S S S N N N

75 32+5 M p2 27 NC ECS 1.56 PPROM S S N N N N S N

76 34 F p2 26 NC ECS 1.34 FD oligoH N S S S S N N N

77 33+6 M p2 23 NC LN 1.35 PPROM S S S S N N N N

78 34+6 M p1 18 NC ECS 2.4 FD N S N S N S N N

79 33+2 F p2 32 NC ECS 2.1 oligo S N S N N N N N cong.M 80 35+6 F p1 18 3 Degree LN 1.89 U N N S N S N N N Nevi 81 34+3 F p3 28 NC ECS 1.67 FD oligoH S S S S S N N N Cutis 82 32+2 F p4 37 NC ECS 1.37 FD N S S N N N S N marmorata 83 34 M p2 29 NC ECS 1.91 PPROM RHD MS with MR S N S N S N N N

Ichthyosis vulgaris, T.labetolol, 84 36 F p1 26 3 ECS 1.79 FD N S S N S S N N family h/o grandma steroid-chronic HT atopy

85 34+3 M p2 25 NC LN 2.05 U S N S N N N N N cause of baby age baby mom consan mode of birth Prenatal comp / physiological epstein miniature congenital sl no parity preterm milia M.crystallina mongolian ET lanugo skin peeling nevi ichthyosis others (weeks) sex age guinity delivery wt drug intake jaundice pearl puberty anomalies delivery 86 33 M p1 22 NC LN 2.4 U N S N S S N N S

87 34 F P3 37 NC LN 2.23 U N S N N S N S N

88 33 M p2 25 NC ECS 2.12 FD oligoH N N N N S N N N Partial CTEV

89 36 M p1 18 NC ECS 1.82 FD S S S S S N N N

90 36 F p3 29 NC ECS 2.05 FD PIH N S N N S N N N

91 34+6 F p1 26 NC ECS 2.55 PPROM S S S S N N N N

92 33 M p2 28 NC ECS 2.2 FD S S S N S N S S Ventral chordee

93 29 M p2 25 NC ECS 1.57 oligo S S S S S N S N

94 36 F p1 19 NC LN 1.66 U oligoH S S S N S N N N

95 31+5 F p1 28 NC ECS 1.71 FD T1DM on insulin N S S N S N N N

HT,nifedipine, 96 36+2 M p1 25 3 ECS 1.95 PPROM N N S N S N N N labetolol, steroids

97 34 F p1 25 NC LN 1.76 U S S N S N N N N exstrophy of 98 35+5 F p2 25 NC ECS 1.87 FD S N S N S N N N bladder,urogenit al anomalies 99 36+3 F p1 24 NC LN 2.5 U N S S N S S N N PIH,Labetolol, 100 32 M p1 28 NC ECS 1.56 FD S S S S S N S N steroids KEY TO MASTER CHART

M - Male

F - Female

P - Parity

NC - Non-consanguinous

C - Consanguinous

LN - Labour naturalis

ECS - Emergency cesarean section

OLIGOH - Oligohydramnios

U - Unknown

FD - Fetal distress

PPROM - Preterm premature rupture of membranes

S - Yes (present)

N - No (absent)

PIH - Pregnancy induced hypertension

HT - Hypertension

IDM - Insulin dependent diabetes mellitus

RHD - Rheumatic heart disease MS - Mitral stenosis MR - Mitral regurgitation

M. crystallina - Miliaria crystallina

ETN - Erythema toxicum neonatorum

Cong. M nevi - Congenital melanocytic nevi PROFORMA

Serial No. Date:

Mother’s Name/Age/Parity : Age/sex of baby:

Address:

Socioeconomic status:

Consanguinity:

Antenatal history:

1st Trimester 2nd trimester 3rd Trimester  Infections  Radiation exposure  Drug intake  Antenatal procedure  Blood VCTC,VDRL  Comorbidities

Natal history:  Mode of delivery:  Birth weight:  Cause of preterm delivery:  Intrapartum complication:

Postnatal care:  Incubator:

 Transcutaneous O2 monitoring:  EEG/ECG Electrodes:  Umbilical artery catheterization:  Needle insertion:  Phototherapy:

General physical examination: Systemic Examination:  CVS:  RS:  Abdomen:  CNS:  Musculoskeletal:  Genitourinary:

Dermatological examination:  Skin: Transient dermatoses: Pigmentary disorders: Vascular disorders: Vesiculobullous disorders: Others:  Scalp, hair:  Palms, soles:  Nails:  Mucosa:

Investigations:  Smears for KOH / Gram staining:  Swabs for pus culture:  Tzanck smear:  Dark field microscopy:

Examination of the family members (parents, sibling):

INFORMATION TO PARTICIPANTS

Title : “A CLINICO EPIDEMIOLOGICAL STUDY ON DERMATOSES IN PRETERM NEONATES”

Investigators : Dr. G. Vinitha Kumari Dr. R. Priyavathani Annie Malathy Dr. Mohamed sajjid Dr. S. Venkatesan

Study Centre : Institute of Obstetrics & Gynaecology, Egmore.

We are conducting a study on “A CLINICO EPIDEMIOLOGICAL STUDY ON DERMATOSES IN PRETERM NEONATES” born in Institute of Obstetrics & Gynaecology, Madras Medical College Chennai and your co-operation may be valuable to us.

The purpose of this study is to determine the prevalence of various dermatoses in the preterm neonates and to study the association with birth weight, gestational age, mode of delivery, consanguinity and systemic associations.

Complete history of the neonate regarding the gestational age, mode of delivery, consanguinity, antenatal history will be taken.

General physical examination, systemic examination, complete dermatological examination including scalp, hair, nails, palms, soles, genitalia and mucosa will be observed

Non –invasive investigations like KOH scraping for candidiasis, gram stain and pus culture, tzanck smear will be taken to confirm diagnosis.

The privacy of the patients in the research will be maintained throughout the study. In the event of any publication or presentation resulting from the research, no personally identifiable information will be shared.

Taking part in this study is voluntary. You are free to decide whether to participate in this study or to withdraw at any time .Your decision will not result in any loss of benefits to which you are otherwise entitled.

The results of the special study may be intimated to you at the end of the study period or during the study if anything is found abnormal which may aid in the management or treatment.

Signature of Investigator Signature of Participant / Guardian

Date: Date:

ஆ தகவ பவ

ஆராசிய தைல: ைற பரசவ பசிள ழைதகள ேதா ேநா பறிய வபரவய ஆ

ஆவாள ெபய : க.வனதா மா

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ஆராசி மய: மகேப ம மகள ேநா நிைலய, எ ெசைன .

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ஏேத சேதக இதா ெவளபைடயாக ேகவக ேக ெத ெகாளலா.

நாக மகேப ம மகள ேநா நிைலயதி ைற பரசவ பசிள

ழைதகள ேதா ேநா பறிய வபரவய ஆைவ நடகிேறா. அத உக

பகள எக ெப உதவ.

இத ஆவ ேநாக:

இவாராசிய தகைடய ழைதைய பறிய அபைட ேகவக (வய,

பரசவ ைற, உறவ திமண, பற எைட) ேககப ம ைகபடக பதி

ெசயப. ெபா உட, ேதா ம ஆவக பேசாதைனெசயப.

இத ஆவகாக ேதைவபடா ேதா சீவ எ ைச இைழ

உளதா என ெபாடாசிய ைஹராஸி ேபா பேசாதைன ெசயப. தக

ழைதைய பறிய தகவக ரகசியமாக பாகாகப.

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ெபயைரேயா அைடயாளகைளேயா ெவளயட மாேடா எபைத ெதவ ெகாகிேறா.

இத ஆவ பேகப உகைடய வபதி ேப தா இகிற. ேம நக

எேநர இத ஆவ இ பவாகலா எபைத ெதவ ெகாகிேறா.

இத ஆவ தக ஆவ இதியேலா அல ஆவ ேபாதிேலா

ெதயபதப.

ஆவாள ைகெயாப

ேததி: பேகபாள/ பாகாவல ைகெயாப

PATIENT CONSENT FORM

Title of the study: “A CLINICO EPIDEMIOLOGICAL STUDY ON DERMATOSES IN PRETERM NEONATES”

Name of the Participant:

Name of the Principal Investigator: DR. G. VINITHA KUMARI.

Name of the Institution: Institute of Obstetrics & Gynaecology, Egmore, Madras Medical College, Chennai-3.

Documentation of the informed consent: I ------have read the information in this form (or it has been read to me). I was free to ask any questions and they have been answered. I am over 18 years of age and exercising my free power of choice, hereby consent to be included as a participant in the study. 1. I have read and understood this consent form and the information provided to me. 2. I have had the consent document explained to me. 3. I have been explained about the nature of the study 4. My rights and responsibilities have been explained to me by the investigator. 5. I agree to co-operate with the investigator and I will inform him/her immediately if I suffer unusual symptoms 6. I have not participated in any research study at any time. 7. I am aware of the fact that I can opt out of the study at any time without having to give any reason and this will not affect my future treatment in this hospital. 8. I hereby give permission to the investigator to release the information obtained from me as a result of participation in this study to the sponsors, regulatory authorities, Government agencies and institutional ethics committee. I understand that they are publicly presented. 9. My identity will be kept confidential if my data are publicly presented. 10. I am aware that if I have any question during the study, I should contact at one of the addresses listed above. By signing this consent form I attest that the information given in this document has been clearly explained to me and apparently understood by me, I will be given a copy of this consent document. Name and signature/ thumb impression of the participant (or legal representative if participant incompetent)

______Name Signature Date

Name and signature of impartial witness (required for illiterate patients): ______Name Signature Date

Address and contact number of the impartial witness: Name and signature of the investigator or his representative obtaining consent: ______Name Signature Date

PLAGIARISM CERTIFICATE

This is to certify that this dissertation work titled “A CLINICO

EPIDEMIOLOGICAL STUDY ON DERMATOSES IN PRETERM

NEONATES” of the candidate DR. VINITHA KUMARI. G. with registration

Number 201630010 for the award of M.D DERMATOLOGY,

VENEREOLOGY & LEPROSY in the branch of XX. I personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 0 percentage of plagiarism in the dissertation.

Guide & Supervisor sign with Seal