An oral nightmare: A rare & refractory Crohn’s Disease case. When nothing seems to work !!!

Dr. Weiner dror Wolfson Medical Center Department of Pediatric Gastroenterology and Nutrition Case:

• R.D - An 18 year old men with Crohn’s disease (CD) diagnosed at the age of 9 years (Paris L3+L4a+p1)

• Under went an Hartmann's procedure at 2012, with a colostomy that was closed 6 month following the operation.

• Followed by another surgery were part of the large bowel was removed and an ileostomy was done.

• Since 2014, evidence of inflamed rectal stump.

• Severe perianal disease with multiple abscesses; trans and inter - sphincteric fistulae - setons placement.

• Steroid dependent; MTX intolerance, Infliximab LOR (immunogenic).

• Started on Adalimumab (40 mg every 2 weeks with a good trough level of around 11 mcg/ml). Case continuous:

• In May of 2017 - multiple oral lesions (deep ulcers), lip swelling and angular cheilitis, exudate can be seen on the pharynx posterior wall.

• Oral and Maxillofacial surgeons: diagnosed the lesions as oral crohn’s disease.

• At biopsy: dense subepithelial lymphoplasmacytic infiltrate with no granulomas. Oral Crohn’s: Orofacial granulomatosis:

• Patients with overt CD and involvement of the • Patients with OFG may present with discrete mouth. ulcers.

• Crohn's disease, oral lesions may be identified • More commonly with lip and facial swelling as in up to 60% of patients where in 5–10% of well as distinct conditions including cases they may be the first manifestation of pyostomatitis vegetans & the Melkersson disease. Rosenthal syndrome.

• There is no clear or expected pattern of • OFG is strongly associated with atopy and food gastrointestinal Crohn's disease presenting with allergy. oral manifestations.

• Greater male predominance, a young age of onset and a higher prevalence of upper gastrointestinal involvement. Types of lesions (OFG)

Fig 1. Lip Lip swelling with fissures Fig 3. Pyostomatitis lesions on the gingival mucosa.

Fig 2. Melkersson - Rosenthal syndrome (MRS). Types of lesions (OCD)

Fig 3. Mucogingivitis in Fig 1. Linear ulceration deep in Fig 2. Cobblestone appearance relation to the maxillary the mandibular vestibule. of the buccal mucosa. permanent incisors. Fig 4. Mucosal tag on the buccal aspect of the gingiva. Types of lesions (OCD)

Fig 5. Angular cheilitis (Meischer Fig 7. Submental lymphadenopathy disease). Fig 6. Buccal abscess. Clinical differentiation: Histopathologic differences:

OCD OFG Differential diagnosis of granulomatous and non- granulomatous oral ulceration: Treatment:

• For many patients with OCD, the oral findings are asymptomatic.

• The majority of lesions resolves spontaneously over time. Oral aphthae Aphthous Labial/facial stomatitis involvment Recurrent Cheilitis microabscesses Periodontal Pyostomatitis Simple ulceration disease MRS

Intralesional Antibiotics 5-ASA or steroids Betamethasone mouth wash Topical Tacrolimus

Dietary restriction* Oral steroids

IFX MTX Thalidomide Colchicine Dapsone TREATMENT ALGORITHM; Gale et al 2016 Back to our case:

5 days of oral Prednisone ADA was stopped, he was started on Salazopyrine & Ustekinumab

Dietary change: low benzoate diet with removal of cinnamon

Colchicine 1 mg/day The oral lesions got better, for ~ 4 weeks But he started to complain of sever dysphagia !!! Dapsone (50 mg a day than 100 mg and than 200 mg a day for a total of 4 weeks So we did an upper endoscopy: So, what is it ?

Esophageal Crohn’s Infection ? But which one: Drug related eruption ? disease ? (Rare 0.2%) Bacterial ? Viral ? Fungal ? (SJS, TEN,DRESS)

Other ? CMV Esophagitis:

• The biopsy showed inclusion bodies (CMV infection)

• And A positive PCR

• He was treated with Ganciclovir for 10 day IV followed by Oral treatment to complete 21 days Second endoscopy after treatment 洛 And the oral nightmare continues:

• About a mouth later – He had Worsening of Buccal Ulcers with swelling of left cheek, suspected parotitis? other?

• Soft tissue US: no enlarged or hyper-vascular parotid glands, with normal appearing lymph- nodes.

• He repeated the oral biopsy: inflamed squamous mucosa with ulceration and granulation tissue; immuno-staining for CMV was negative, And no granulomas were seen ! To conclude:

1) Sever crohn’s disease involving the proximal 1/3 of the small bowel

2) Sever oral involvement.

3) Sever esophageal disease.

4) Sever peri-anal involvement.

5) Anti – TNF – loss of response, on Stelara every 4 weeks !!! Thank you for listening