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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Manuscript Accepted Early View Article
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TYPE OF ARTICLE: Case Report 1
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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
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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
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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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TITLE: Respiratory papillomatosis in a case of Carmi Syndrome: An unusual 64
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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TITLE: Respiratory papillomatosis in a case of Carmi Syndrome: An unusual 95
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
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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
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Figure 6: Voiding cystourethrogram showing dilatation and elongation of posterior 290
urethra and bladder trabeculation 291
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