journal name: international journal of case reports and ... is a of the ... 70 congenital pyloric...

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Early View Article: Online published version of an accepted article before publication in the

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Journal Name: International Journal of Case Reports and Images (IJCRI)

Type of Article: Case Report

Title: Respiratory papillomatosis in a case of Carmi Syndrome: An unusual presentation

Authors: Mitra Sandipta, Hazra Sayan, Sengupta Arunabha

doi: To be assigned

Early view version published: May 2, 2017

How to cite the article: Sandipta M, Sayan H, Arunabha S. Respiratory papillomatosis in

a case of Carmi Syndrome: An unusual presentation. International Journal of Case

Reports and Images (IJCRI). Forthcoming 2017.

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TYPE OF ARTICLE: Case Report 1

2

TITLE: Respiratory papillomatosis in a case of Carmi Syndrome: An unusual 3

presentation 4

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AUTHORS: 6

Mitra Sandipta1, Hazra Sayan2, Sengupta Arunabha3 7

8

AFFILIATIONS: 9

1MBBS, Junior Resident, Dept. of Otorhinolaryngology and Head Neck Surgery, 10

Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, 11

India, [email protected] 12

2MBBS, Junior Resident, Dept. of Otorhinolaryngology and Head Neck Surgery, 13

Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, 14

India, [email protected] 15

3MS, DLO, Professor and Head of the Department, Dept. of Otorhinolaryngology and 16

Head Neck Surgery, Institute of Post Graduate Medical Education and Research, 17

Kolkata, West Bengal, India, [email protected] 18

19

CORRESPONDING AUTHOR DETAILS 20

Dr. Sandipta Mitra 21

618, ‘O’ Block, New Alipore, Kolkata, West Bengal, India, 700053 22

Email: [email protected] 23

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Short Running Title: A queer presentation of Carmi syndrome 25

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Guarantor of Submission : The corresponding author is the guarantor of 27

submission. 28

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SUMMARY 33

Carmi syndrome is a rare disease affecting multiple organ systems. Not much has 34

been documented in literature about this disease. Respiratory papillomatosis, on the 35

other hand, is a common benign disorder affecting the respiratory tract of children. 36

Here, we report an interesting case of Respiratory papillomatosis along with 37

posterior urethral valve in a 9-year-old male child with features of Carmi syndrome. 38

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presentation 65

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ABSTRACT 67

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Introduction 69

Congenital pyloric atresia with junctional epidermolysis bullosa and congenital cutis 70

aplasia is known as Carmi syndrome. 71

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Case Report 73

We report a case of squamous papilloma of the respiratory tract with posterior 74

urethral valve in a case of Carmi syndrome. 75

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Conclusion 77

Such presentation is extremely unusual and has not been documented yet. 78

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Keywords: Carmi syndrome, pyloric atresia, epidermolysis bullosa, respiratory 80

papilloma, posterior urethral valve 81

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presentation 96

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INTRODUCTION 98

Carmi syndrome is an extremely rare disease manifesting with congenital pyloric 99

atresia and junctional epidermolysis bullosa, with the inheritance pattern being 100

autosomal recessive. [1, 2] 101

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CASE REPORT 103

A preterm male infant was delivered by lower uterine Caesarean section, with a 104

history of polyhydramnios in the mother. The newborn infant developed repeated 105

episodes of vomiting with regurgitation of feeds since birth. A diagnosis of congenital 106

pyloric atresia was made for which he underwent gastroduodenostomy(Figure 1) on 107

the fifth day of life. He also developed bullous lesions over the trunk and extremities, 108

with new lesions developing with trivial trauma (Figure 4). At six months of age, the 109

child developed poor stream of urine with discharge of whitish flecks with fever. 110

Urine culture was positive for Pseudomonas aeruginosa, sensitive to Gentamicin. 111

Ultrasound showed hydronephrotic changes in both kidneys with dilatation of 112

bilateral ureters. He was diagnosed to have posterior urethral valve(Figure 6) for 113

which vesicostomy(Figure 2) had to be done after attempts of cystoscopy guided 114

valve fulguration were deemed ineffective in a setting of recurrent urinary tract 115

infection and hydronephrosis. The child presented with respiratory distress and 116

hoarseness at four and a half years of age. Thereafter, direct laryngoscopy was 117

done which revealed multiple masses occupying bilateral false cords, left ary-118

epiglottic fold and anterior commissure (Figure 5). The masses were firm, fleshy, 119

pedunculated and did not bleed on touch. Biopsy was taken and surgical excision of 120

the masses was done. The histopathology report revealed squamous 121

papilloma(Figure 7). The child again presented with acute severe respiratory distress 122

with cyanosis two months following discharge, for which emergency tracheostomy 123

had to be done. Attempts of weaning were tried but the child was unable to tolerate 124

it. At present, the child is nine and a half years old, tracheostomized, school-going 125

with age-appropriate neurodevelopment. His six-and-a-half-year-old sister underwent 126


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gastroduodenostomy for congenital pyloric atresia on 21st day of life and 127

vesicostomy for posterior urethral valve at two years of age. She was also diagnosed 128

with junctional epidermolysis bullosa at four years of age. Interestingly, the mother 129

suffered from polyhydramnios during the birth of her second child also. There is 130

history of sibling death within first week of life in his father’s generation following a 131

blistering disorder. 132

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DISCUSSION 134

Respiratory papillomatosis is a benign tumor of the respiratory tract, usually caused 135

by Human Papilloma Virus 6 or 11 infection, often presenting with hoarseness of 136

voice, stridor and acute airway obstruction requiring emergency tracheostomy. The 137

reported incidence of recurrent respiratory papillomatosis in a population based 138

Danish study is 3.62 per 100 000[3]. Such population based data in the Indian 139

subcontinent is limited. Hence, to strengthen the database, a national registry [4] has 140

been introduced. Surgical excision of the papillomas remain the mainstay of 141

treatment, though medical therapy including intralesional antivirals [5] and HPV 142

vaccines [6] have also been tried. Here we report an unusual case of respiratory 143

papillomatosis and posterior urethral valve in addition to junctional epidermolysis 144

bullosa with congenital pyloric atresia, which constitute Carmi syndrome. JEB with 145

congenital pyloric atresia has been associated with mutation in the α6β4 integrin 146

genes (ITGA6, ITGB4)[2], leading to the formation of blisters which rupture on 147

mechanical insults. Congenital heart disease [7] has also been reported in Carmi 148

syndrome. Peptic perforation [8] and enterocolitis [9] are known complications of 149

Carmi syndrome. Prenatal diagnosis of Carmi syndrome is made by 150

ultrasonographic findings like polyhydramnios, gastric dilatation, “snowflake sign” in 151

amniotic fluid and complete separation of chorioamniotic membrane [10]. 152

Preimplantation genetic detection [11] and immunofluorescence assisted villous 153

trophoblast analysis [12] have also been as diagnostic tools. Although management 154

of this rare disorder is early diagnosis and timely symptomatic intervention, gene 155

therapy may yield promising results and creates ample scopes of research. 156

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CONCLUSION 159

Respiratory papillomatosis is a common disease in the paediatric population that 160

may have syndromic association as highlighted in the case report above. Hence 161

formulation of a multidisciplinary approach to the diagnosis of respiratory 162

papillomatosis with thorough systemic examination, keeping such multi-system 163

affection in mind is imperative to rule out any syndromic association, that may be 164

often missed. Moreover, further studies may help to expand the spectrum of 165

symptoms that define this rare disease-Carmi syndrome. 166

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CONFLICT OF INTEREST 168

None 169

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AUTHOR’S CONTRIBUTIONS 171

Dr. Sandipta Mitra 172

Group1 - Conception and design, Acquisition of data, Analysis and interpretation of 173

data 174

Group 2 - Drafting the article, Critical revision of the article 175

Group 3 - Final approval of the version to be published 176

177

Dr. Sayan Hazra 178

Group1 - Conception and design, Acquisition of data, Analysis and interpretation of 179

data 180

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Dr. Arunabha Sengupta 182

Group 3 - Final approval of the version to be published 183

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REFERENCES 185

1. Carmi R, Sofer S, Karplus M, Ben-Yakar Y, Mahler D, Zirkin H, Bar-Ziv J, 186

Opitz JM. Aplasia cutis congenita in two sibs discordant for pylori atresia. Am 187

J Med Genet 1982; 11:319–28. 188

2. Mutlu M, Kalay E, Dilber B, Aslan Y, Dilber E, Almaani N, McGrath JA. Pyloric 189

atresia-junctional epidermolysis bullosa syndrome showing novel c.4505-190


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4508insACTC mutations in integrin b4 gene (ITGB4). Turk J 191

Pediatr. 2015;57(4):385-387. 192

3. Larson DA, Derkay CS. Epidemiology of recurrent respiratory papillomatosis. 193

APMIS 2010;118: 450–454. 194

4. Mishra A, Singh D B, Verma V. Recurrent respiratory papillomatosis: The 195

need for an Indian national registry. J Laryngol Voice 2011;1:36-7 196

5. Murono S, Nakanishi Y, Tsuji A, Endo K, Kondo S, Wakisaka N, Yoshizaki T. 197

Intralesional cidofovir injection for recurrent respiratory papillomatosis in 198

Japan. Auris Nasus Larynx. 2016;43(5):541-5. 199

6. Hermann JS, Weckx LY, Monteiro Nürmberger J, Santos Junior GF, Campos 200

Pignatari AC, Nagata Pignatari SS, Effectiveness of the human papillomavirus 201

(types 6, 11, 16, and 18) vaccine in the treatment of children with recurrent 202

respiratory papillomatosis, Int J Pediatr Otorhinolaryngol. 2016;83:94-8. 203

7. Aydin M, Zenciroglu A, Yaman A, Orun UA, Arda N, Colak AG, Okumus 204

N, Ipek MS, Ceylaner S, Carmi syndrome with congenital heart defects, Am J 205

Med Genet A. 2010;152A (8):2120-2. 206

8. Joshi M, Krishnan L, Kuruvila S, Large gastric perforation in carmi syndrome: 207

a morbid complication in a rare association, J Neonatal Surg. 2012;1(4):57 208

9. Prabhu V, Sankar J, Srinivasan A, Sathiyasekaran M, Desquamative 209

enterocolitis: an intestinal variant of Carmi syndrome presenting as protein-210

losing enteropathy, Indian J Gastroenterol. 2008; 27(5):215-6. 211

10. Dural O, Acar DK, Ekiz A, Aslan H, Polat İ, Yildirim G, Gulac B, Erdemoglu 212

Y, Cay A, Hacıhasanoglu O, Prenatal ultrasound findings and a new 213

ultrasonographic sign of epidermolysis bullosa with congenital pyloric atresia: 214

a report of three cases, J Med Ultrason (2001). 2014; 41(4):495-8. 215

11. Ozge A, Safak H, Ebru H, Evrim U, Bilge SE, Leyla O, Kemal KA, Volkan B, 216

First successful preimplantation genetic diagnosis of epidermolysis bullosa 217

with pyloric atresia: case study of a novel c.4505-4508insACTC mutation, J 218

Assist Reprod Genet. 2012;29(4):347-52. 219

12. D'Alessio M, Zambruno G, Charlesworth A, Lacour JP, Meneguzzi G, 220

Immunofluorescence analysis of villous trophoblasts: a tool for prenatal 221


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diagnosis of inherited epidermolysis bullosa with pyloric atresia, J Invest 222

Dermatol. 2008; 128(12):2815-9. 223

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FIGURE LEGENDS 225

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Figure 1: Child with tracheostomy tube in-situ with scar of gastroduodenostomy 227

incision 228

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Figure 2: Bullosa involving right limbal conjunctiva 230

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Figure 3: Scar of vesicostomy 232

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Figure 4: Healed scars of ruptured bullosa over extremities 234

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Figure 5: Fleshy masses in bilateral false cords, left aryepiglottic fold and anterior 236

commissure 237

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Figure 6: Voiding cystourethrogram showing dilatation and elongation of posterior 239

urethra and bladder trabeculation 240

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Figure 7: Photomicrograph showing multiple squamous papillae (H and E, x40) 242

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FIGURES 254

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Figure 1: Child with tracheostomy tube in-situ with scar of gastroduodenostomy 258

incision 259

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Figure 2: Bullosa involving right limbal conjunctiva 263

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Figure 3: Scar of vesicostomy 267

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Figure 4: Healed scars of ruptured bullosa over extremities 271

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Figure 5: Fleshy masses in bilateral false cords, left aryepiglottic fold and anterior 277

commissure 278

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Figure 6: Voiding cystourethrogram showing dilatation and elongation of posterior 290

urethra and bladder trabeculation 291

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Figure 7: Photomicrograph showing multiple squamous papillae (H and E, x40) 295

journal name: international journal of case reports and ... is a of the ... 70 congenital pyloric...

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