A case of Kindler Syndrome presenting with dysphagia.

(Dysphagia in Kindler syndrome)

Nasser Ebrahimi Daryani*1, mahsa abbaszadeh2

*Corresponding Author: Nasser Ebrahimi Daryani

Flour2, no.130, Shahid Naseri Street, Valiasr Ave, Tehran, Iran(phone number: 021-88793896)

1.Professor, Department of internal medicine, Division of Gastroenterology, Imam Khomeini hospital, Tehran university of medical science, Tehran, Iran

2. Resident, Department of internal medicine, Imam Khomeini hospital, Tehran University of medical science, Tehran, Iran

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Abstract

Kindler syndrome is a rare hereditary disorder which involves skin and mucosal membrane predominantly. Its characteristic manifestations include acral skin blistering, progressive photosensivity, skin atrophy and poikiloderma which begin from infancy and childhood. Urethral, anal, esophageal, mouth and laryngeal mucosa may involve in this syndrome, so periodontitis and gingival involvement, anal, esophageal or urethral strictures can be seen in this disease.

Although gastrointestinal tract involvement in patients with Kindlersyndrome is possible but seems to be rare in the literature. We reported a 34 year old man with kindler syndrome who had referred with dysphagia.Upper gastrointestinal endoscopy revealed an esophageal web in upper third of esophagus. Endoscopic Dilatation of esophageal web was done by using mechanical dilating bougie. 2 months after esophageal dilatation we found significant improvement in patient’s dysphagia according to completing the validated Mayo Dysphagia Questionnaire (MDQ).

Keywords:Kindler Syndrome, dysphagia, Gastrointestinal Endoscopy, dilatation, esophageal stenosis

Introduction

Kindler syndrome was originally described in 1954 by Theresa Kindler. (1) It is a rare autosomal recessive disorder that mostly affects skin and mucosal membrane. Defect in KinD1 gene which is localized on chromosome 20P 12.3 is recognized to have the main role in causing Kindler syndrome. This gene encodes a 677-aminoacid protein, Kindlin1 which is a membrane associated structural and signaling protein and defect of it leads to the dissociation of the cellular actin cytoskeletal from the extracellular matrix.

Disease usually present with the skin manifestation in infancy and childhood which include blister formation, progressive poikiloderma, photosensivity and diffuse cutaneous atrophy (particularly on the dorsal hands or feet).(2) Both blistering and photosensivity may decrease with age. Mucosal membrane can involve in this disease and leads to esophageal, vaginal and urethral strictures.

Some other features including dental problems, nail dystrophy, webbing of fingers and ophthalmic abnormalities may or may not be present. The occurrence of squamous cell carcinoma and bladder transitional cell carcinoma has been reported.

Morbidity and mortality of disease are mostly related to secondary infectious arising from blisters and bullas. Disease occurs with equal rate in male and female, with no different in races. (3)

gene sequencing of the FERMT1 gene (KIND1 gene), is the current gold standard for diagnosis, but up to 30 percent of patients who present with features suggestive of the diagnosis do not have a mutation in this gene.(4)

Treatment is mainly symptomatic and limited to management of the symptoms and complications of the disease with consultation of dermatologist, geneticist, dentists, ophthalmologist and gastroenterologist.

We report a case of a 34-year-old man who developed progressive dysphagia due to esophageal stricture and was treated by endoscopic dilatation.

Case report

A 34-year-old man was referred to our clinic with a history of skin lesions from infancy which includes blister formation, progressive poikiloderma,reticular pigmentation,photosensivity;webbing of the fingers and the toes and cutaneous atrophy which limits his hand movements. He also suffered from nail dystrophy, unilateral hearing loss in the right ear, reduced tear secretion and xerophthalmia, periodontitis and progressive dysphagia.

He was under observation with a dermatologist from childhood. He was performed a histopathological survey from skin specimen which was nonspecific and included epidermal atrophy, capillary dilatation and upper dermal edema. The patient had not given consent for the performance of genetic analysis yet. He was treated conservatively with emollients; sunprotective creams and oral retinoids (cap ACITRETIN or Neotigasone 10mg, 25mg from the age of 11).

He was complaining of progressive dysphagia which was started at the age of 18.He could swallow fluid food easily, but he had difficulty in swallowing solid foods. He was very upset that hecould notswallow his tablets or capsules at all. He noted that dysphagia was predominantly localized to the chest and it was persisted through these years with variable severity.

He had not any problem with defecation and anal movements. He had no significant finding in her personal and familial medical histories and there were not any skin disease in his family.

In physical examination he had poikiloderma and skin atrophy of the hands and feet which limit her hands and feet movements. Sclerodactyly of the fingers and toes was present and most of the nails were dystrophic (figure 1). Reticular erythema of the face, affecting mostly the cheeks was the only manifestation of disease on the face. Trunk and abdomen were intact. There was not any significant problem in his oral cavity or pharynx which explains swallowing problems.

The history of progressive dysphagia in this patient was strongly suggestive of esophageal problems which made us to perform upper gastrointestinal endoscopy.

In upper gastrointestinal endoscopy he had an esophageal web in upper third of esophagus(figure 2).Esophageal dilatationwas done by using mechanical dilating bougie(Savary).Dilatation was started by using Savary No:9mm and extended to the 14mm.(9mm, 11mm, 12.8mm, 14mm).

2 months after esophageal dilatation we evaluate patient’s dysphagia with completing the validated Mayo Dysphagia Questionnaire (MDQ) and found significant improvement in patient’s symptoms. Nowhe was able to swallow her tablets or capsules easily.

Discussion

More than 100 cases of kindler syndrome have been reported worldwide since the first description of disease in 1954. (3) One of the biggest studies about 26 Kindler patients in the year 2004 established that all of them share 4 major clinical manifestations including acral blister, progressive poikiloderma, severe skin atrophy and increased photosensivity. (3)

Angelova-Fischer article about Kindler syndrome in 2005 proposed a set of clinical diagnostic criteria for this syndrome. He divided disease’s clinical manifestations to 3 groups: major, minor and associated findings. Presence of the 4 major criteria makes the diagnosis certain. The presence of 3 major and 2 minor criteria makes the diagnosis probable. Major criteria include acral blistering, progressive poikiloderma, skin atrophy, increased photosensivity and gingival involvement. Minor criteria include Syndactyly and mucosal involvement including urethral, anal, esophageal or laryngeal. Associated findings include nail dystrophy, ectropion of the lower lid, keratoderma, pseudoainhum, leucokeratosis of the lips, squamous cell carcinoma, anhidrosis, skeletal abnormalities, dental caries and periodontitis. (5)

According to mentioned criteria our patient demonstrates 4 major criteria and the diagnosis was certain. (Acral blistering, progressive poikiloderma, skin atrophy and photosensivity)

Gastrointestinal manifestations are not as common as skin involvement in kindler syndrome. Aside from esophageal or anal stenosis, GI tract involvement seems to be rare in this syndrome. Here we review some gastrointestinal manifestations of the disease that has been reported in the literature.

In 2006 in the article of Elk Sadler et al. from Australia,they state besides esophageal and anal stenosis, nocases with severe gastrointestinal tract involvementhave been described before their article. They mentioned the limited accessibility of gastrointestinal tractepithelia and the very low number of patients as the reasons for that.

They reported an infant with proven Kindler syndrome in Australia who presented bloody colic stool in the first postnatal week. Gastroduodenoscopy and colonoscopy were performed for him. Biopsy specimens from upper gastrointestinal tract showed normal histology. But in Histological assessment of mucosa of the descending and sigmoid colon and the rectum, erosions and ulcers with pseudomembranous alterations of an overall highly vulnerable mucosa was seen. The article said although we can consider the bloody diarrhea a part of other common diseases, but it is more likely to be due to kindler syndrome.

It also reported a 49 year old man who underwent partial resection of the small bowel because of stenosis of it. First it was thought to be caused by Crohn’s disease but finally it remains unclear whether this gastrointestinal tract involvement was caused by Crohn disease or Kindler syndrome, which was diagnosed 4 years after the resection.

After describing these two cases they mentioned that it is feasible that thegastrointestinal tract alterations inKindler syndrome couldbe observed more frequently than described. It said that considering that the highest expression of the KIND1 gene can be foundin keratinocytes, colon and kidney, it is proposed that gastrointestinal tract involvementshould be looked at more frequently in Kindlersyndrome.(6)

In Lai-Cheong article in 2008 about GI manifestations of Kindler syndrome, it said that anal and esophageal stenosis is frequently seen. It also mentioned patients can develop gastrointestinal symptoms such as severe colitis and bloody diarrhea. About the management of GI tract involvement of Kindler syndrome it said esophageal stenosis may require esophageal dilatation. In cases with severe esophageal dysfunction, temporary parenteral nutrition may be indicated.(4)

In Mansur A.Tulin literature in 2007 we have a 16 year old female of kindler syndrome who suffers from dysphagia, weight loss and anemia. Esophagoscopy and a barium esophagogram confirmed esophageal stenosis and web formation. For treatment she has been scheduled to undergo a series of esophageal dilatation sessions, following temporal parenteral nutrition to improve her general condition. (7)

The adult esophageal length is about 18-26cm and is anatomically divided into the cervical and thoracic. Its diameter is2cm in the anteroposterior plane and 3cm in the lateral plane. Patients have solid food dysphagia when its lumen is narrowed to <13mm causing by strictures, web, rings and other structural abnormalities. It can also occur with larger diameters in the setting of poorly masticated food or motor dysfunction. Circumferential lesions are more likely to cause dysphagia than are lesions that involve only a partial circumference of esophageal wall. (8)

Different endoscopic techniques are currently available for therapy of esophageal strictures or webs. Three general types of dilators are commonly in use including (1) mercury or tungsten-filled bougies (Maloney or Hurst), (2) wire-guided polyvinyl dilators (Savary Gilliard or American), and (3) TTS (‘‘through-the-scope’’) balloon dilators. (9) The Maloney type bougies have a taperedtip and can be passed either blindly (10) or under fluoroscopic control. This type of dilator is used for simple strictures with a diameter of 12 to 14mm. The risk of esophageal perforation may be higher with blind passage of Maloney dilators than with Savary or TTS balloons, particularly in patients with a large hiatal hernia, a tortuous esophagus, or those with complex strictures. (11) Savary and American dilators are passed over a guidewire that has been positioned with the tip in the gastric antrum, with or without fluoroscopic guidance (12). There are a variety of available TTS balloon dilators available in either single or multiple diameters that may be passed with or without wire guidance.

We performed esophageal dilatation by using Savary 9mm and extended it to 14mm. after 2 months patient was more satisfied by swallowing function according to the answering the validated Mayo Dysphagia Questionnaire (MDQ).

Kindler is a chronic and severe syndrome that its treatment is mainly symptomatic. We should help these patients by improving their lifestyle through reducing their symptoms and complications of the disease.

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