Key words

Carmi syndrome, junctional epidermolysis bullosa, pyloric atresia

Author Details

1. Dr Sindhu Desabandhu,Resident, Department of Dermatology,Sri Ramachandra University,Porur, Chennai
2. Dr Aditya Kumar Bubna, (Corresponding author)Assistant Professor, Department of Dermatology,Sri Ramachandra University,Porur, Chennaie-mail: zimbabwa21@gmail.com
3. Dr MahalakshmiVeeraraghavan,Professor, Department of Dermatology,Sri Ramachandra University,Porur, Chennai
4. Dr SudhaRangarajan,Professor, Department of Dermatology,Sri Ramachandra University,Porur, Chennai

Introduction

Epidermolysis bullosa(EB) comprises an inherited group of disorders characterized by the development of skin blisters on meagre trauma or skin traction[1]. EB is further classified as EB simplex, junctional EB and the dystrophic type[2]. Out of the three variants, it is the junctional type that is associated with pyloric atresia(PA), though rarely PA may be associated with the simplex variant also. When junctional EB and PA exist together it is referred to as Carmi Syndrome(CS), which has an exceeding high mortality rate. However with early surgical intervention there have been few rare cases that have survived, with regression of blistering as the child grows.

Case Report

A 4 day old female neonate was referred to the department of Dermatology for evaluation of blisters over the sites of venepuncture. The primary reason for the child being brought to the hospital was for persistent vomiting which started 2 days after birth. The baby was a pre-term child, born at 36 weeks of gestation to 3rd degree consanguineous parents. At birth the child weighed 2.5 kg, and she was the third child of her parents. Her previous two siblings had died 5 days and 10 days after birth, owing to pyloric atresia, despite surgical correction. On examination epigastric fullness and visible gastric peristalsis were noted. A dermatologic examination revealed a 5x6 cm bulla over the right knee [Figure 1], two haemorrhagic bullae, one measuring 2x3 cm and another 2x2 cm, located over the dorsa of the left hand and the left wrist respectively, [Figure 2] and areas of post inflammatory hypopigmentation with a 1x1 cm sized bulla and two vesicles in the left retro-auricular region [Figure 3]. A complete investigative workup revealed the following abnormalities. Hypokalemia was present, in the serum electrolyte assessment, with metabolic alkalosis, in the arterial blood gas analysis. A dilated gastric shadow with the classical single bubble appearance [Figure 4] was witnessed on abdominal radiography, and a skin biopsy of the bulla on the wrist demonstrated a split at the level of the dermo-epidermal junction with a pauci-inflammatory infiltrate [Figure 5]. Immune electron microscopy could not be done due to lack of facilities in our institute. With these findings a diagnosis of CS was made. Patient was taken up for an emergency laparotomy. During the procedure a dilated stomach [Figure 6] secondary to a solid cord, obstructing the pyloric canal [Figure 7], was identified. A gastroduodenostomy was performed [Figure 8]. After 5 days of the surgery, oral feeds were gradually started. The patient tolerated the oral feeds well. Over the blisters, the use of a topical antibiotic cream was suggested and avoidance of pressure and trauma were the instructions given to her parents. At two months of follow up the patient weighed 3.5 kg and had no difficulty while taking oral feeds. Skin lesions had healed well leaving behind milia and parchment like scars [Figure 9]. No developmental delay could be identified. At 7 months of follow up the child weighed 7 kg and was doing well [Figure 10]. No new blisters were identified. Now the child is nine years of age and is doing perfectly fine. There have been no recurrence of cutaneous lesions with no gastrointestinal symptoms.

Discussion

PA and EB are very rare autosomal recessive disorders. The concurrent occurence of the the two, was first described in 1968 by Swinburne and Kohler[3,4]. However it was Carmi who elucidated the pathophysiology of this disorder and hence the name, CS[5]. Though PA is the most frequent gastrointestinal atresia associated, the occurance of duodenal atresia with EB has also been reported[6]. The incidence of PA is estimated to be 1/100,000 live births[7] and the combination of EB with PA is rarer still. Ninety three cases of EB with PA have been reported in literature till date[8]. The gene for CS has been identified to be ITGA6, located on the long arm of chromosome 2 and ITGB4 located on the long arm of chromosome 17, which encodes the hemidesmosomal protein alpha6beta4 integrin that helps in maintaining the dermo-epidermal attachment. A mutation occurring here results in a compromise of the adhering between the dermis and the epidermis which clinically presents in the form of blisters[9]. Around 15% of cases of CS result from mutations in the PLEC gene[10] which instructs in the making of plectin. Plectin like alpha6beta4 integrin, helps maintain the dermo-epidermal integrity. Altered plectin makes the skin less resistant to friction and minor trauma heralding cutaneous blisters. Neonates with CS present with non-bilious vomiting as the first symptom, which may even occur immediately after birth. A plain radiograph of the abdomen with an air filled distended stomach and an otherwise gasless abdomen helps in the diagnosis of PA[11]. Cutaneous blistering may not appear even as late as 48 hours after birth. Other features occurring due to the disrupted intestinal mucosa include malabsorption, bloody diarrhoea and protein losing enteropathy. CS patients may also present with urinary[12], pulmonary and ocular abnormalities[13]. Management includes a multidisciplinary approach. Apart from the surgical correction of PA, a meticulous minimal touch principle is advocated for the skin, along with antibiotics and antiseptics to prevent secondary impetiginisation. A proper nutritional support is another important aspect of managing these patients. During surgery precautions to prevent any form of trauma is minimized, like coating the face mask with a petrolatum jelly gauze, meticulous intubation using a no cuff endotracheal tube and removal of the adhesive components of the electrodes while performing an ECG. Appropriate post surgical care is also advocated. Our patient had a solid type of PA, for which the atretic segment was excised and a gastroduodenostomy was performed. In case of a short atretic segment the surgery of choice would have been Heineke Mikulicz pyloroplasty. To conclude, CS is a lethal condition with death being a universal result. Inspite of timely surgical intervention, patients are able to survive only for the first few months of life[14].However there have been reports wherein patients with CS have shown considerable improvement and have survived post infancy as reported by Ha et al[15], Hayashi et al[16] and Sahebpoor et al[17].Our case too, survived the post infancy stage and at present is nine years of age with complete remission of cutaneous blistering and no systemic problems.Though CS is a lethal condition there have been anecdotal reports of its favourable outcome and so we present this case for its rarity.

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