Late-onset ‘sloughing esophagitis’ (esophagitis dissecans superficialis) associated with bullous pemphigoid

Abstract

Pemphigus is a rare autoimmune disease that causes blistering of the skin and oral mucosa. In bullous pemphigoid (BP), skin involvement is predominant, whereas oesophageal involvement is rare, compared with other blistering diseases. We present, herein, the case of a 67-year-old man with a history of successfully treated BP that 2 years later developed progressive dysphagia, unintentional weight loss and iron deficiency anaemia. An endoscopy with biopsies was performed, and its findings were consistent with ‘sloughing esophagitis’ (esophagitis dissecans superficialis) associated with BP. Oesophageal involvement was present during the first weeks, making our case unusual due to the isolated oesophageal symptoms that developed 24 months later.

Background

Autoimmune blistering diseases of the pemphigoid type (bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, lichen planus pemphigoides and bullous lupus) are characterised by subepidermal blisters with circulating autoantibodies against components of the basement membrane zone.¹ This is in contrast to pemphigus vulgaris (PV) and related disorders, which demonstrate intraepidermal acantholysis and antibodies against desmosomal components. PV is usually a mucosal­-dominant disease with mucosal lesions but minimal skin involvement. In contrast, BP skin compromise is predominant, whereas oesophageal involvement is rarely seen.¹

In 1892, Rosenberg coined the term esophagitis dissecans superficialis (EDS) to describe a rare and severe endoscopic finding characterised by sloughing of large fragments of oesophageal mucosa lining. Its usual symptoms are dysphagia, odynophagia and heartburn.^2–4 Haematemesis or vomiting oesophageal casts rarely occurs. The causes of EDS include idiopathy, medications (bisphosphonates, non-steroidal anti-inflammatory drugs and potassium chloride), hot beverages, chemical irritants, coeliac disease, collagen diseases and autoimmune bullous dermatoses. When EDS is associated with bullous dermatoses, such as BP, oesophageal involvement is usually present during the first weeks.^3–5 The pathophysiology and strong relationship between those two entities has gained interest in recent years.

Case presentation

A 67-year-old man had a medical history of BP with skin involvement but no evidence of oesophageal involvement 2 years prior. At that time, subepidermal bullae were seen, with preserved dermal papillae and marked dermal and epidermal eosinophil infiltration, consistent with BP. The ELISA test revealed anticollagen XVII and BP230 antibodies in the patient’s serum, but no antidesmoglein 1 or 3 antibodies were detected. Due to the lack of oesophageal symptoms, the patient did not undergo upper gastrointestinal endoscopy to assess involvement of the oesophagus. He was hospitalised in the intensive care unit and treated with intravenous steroids (intravenous methylprednisolone pulses 1 g for 5 days) followed by oral prednisone 1 mg/kg. After 2 weeks, improvement of the skin was noted, and steroid reduction was then prescribed during the following 6 months. After 18 months, the patient was asymptomatic with no skin lesions. Thereafter, he developed progressive dysphagia, first to solids and then to liquids, accompanied by unintentional weight loss of approximately 40 lb in 6 months. He was referred to our institution and no skin involvement was found at that time. Anaemia (haemoglobin of 11.8 g/L) and hypoalbuminaemia (3.1 g/dL) were reported. An upper endoscopy (figure 1) revealed multiple aphthous ulcers on the soft palate, extensive reddish erosion, whitish linear sheets and concentric stricture of the oesophagus. In the distal oesophagus, multiple stripped areas of the mucosa were bleeding and concentric strictures related to sloughing esophagitis were found at some points. The biopsies further confirmed the aetiology as pemphigoid involvement of the oesophagus. Specifically, the oesophageal epithelium had a thin layer of parakeratosis and a small intraepithelial bulla (figure 2).

Figure 1.

(A) Endoscopy showing aphthous ulcers on the soft palate. (B) Extensive reddish erosion, whitish linear sheets and concentric stricture of the oesophagus. (C) Endoscopy showing stripped mucosa with bleeding and long linear mucosal break. (D) Oesophageal concentric stricture related to sloughing esophagitis.

Figure 2.

Histopathologic examination of the biopsied oesophageal mucosa showed findings consistent with esophagitis dissecans superficialis (sloughing esophagitis), which are parakeratosis, a hyperplastic basal layer, ‘two-toned appearance’, acantholysis, spongiosis and low lymphocytic infiltrate. Periodic acid–Schiff stain was negative for microorganisms. (A) Epithelium with parakeratosis and ‘two-toned appearance’ (H&E stain, ×40). (B) Oesophageal epithelium with thin layer of parakeratosis (two-toned appearance) and a small intraepithelial bulla (left side) with acantholytic cells in the interior (H&E, ×20).

Outcome and follow-up

Given those findings, the patient was restarted with oral prednisone 50 mg/day, and after 8 weeks, the oesophageal dysphagia has improved. Nutritional advice and iron supplementation were also provided.

Discussion

‘EDS’, also called ‘sloughing esophagitis’, is a very rare benign, desquamative, chronic autoimmune disorder, with a self-limited process. Its pathogenesis is poorly understood, and the disease usually affects children and adults over 50 years of age. It is characterised by the sloughing of large fragments of the oesophageal mucosa, followed by vomiting or regurgitation of the oesophageal cast.² Lazenby was the first to use the term ‘sloughing esophagitis’, when he showed amazing histologic changes during the 2005 Digestive Disease Week. However, for all practical purposes, they are managed as the same entity.³

Histologically, our case of EDS confirmed by endoscopy and biopsy showed a constellation of findings, which, if found in isolation, may not have been specific. Parakeratosis is the most frequent histologic finding in this pathology and can occur in other conditions, such as stenosis that covers the oesophageal mucosa, thermal, physical or chemical injury, mucosal lesions associated with drugs, gastro-oesophageal reflux disease (GERD), lichen planus, prolonged intubation, achalasia and bacterial or fungal infections. Our case also presented with the previously described characteristics of a hyperplastic basal layer and acantholysis. The presence of eosinophils and lymphocytes is frequently found in GERD and eosinophilic esophagitis, and so a differential diagnosis including those entities is necessary.^{3 4}

One of the most interesting features is the presence of intercellular oedema (spongiosis), which has been reported as an infrequent finding. Other findings described in EDS include bullae formation, a ‘tombstone appearance’, intraepithelial cysts, bacterial and fungal colonies, separation of the mucosa from the submucosa, microabscesses, pyknotic nuclei, detached strips of squamous epithelium and cell necrosis.⁴

Endoscopic features of EDS are stripped mucosa with bleeding, total desquamation of the oesophageal mucosa without bleeding, long linear mucosal break, vertical fissures and circumferential cracks with peeling, whitish mucosa with extensive bleeding and exudative esophagitis. Endoscopic studies in patients with PV have shown a high incidence (46%–87%) of oesophageal lesions, such as local erythema, erythematous longitudinal lines and blisters and ulcers, as in the present case. It is important to distinguish those lesions from candidal, herpetic and peptic esophagitis, which are frequent in pemphigus patients receiving steroids and immunosuppressive drugs.⁵

To establish the diagnosis of EDS, it is absolutely necessary to work hand in hand with the clinical physician and consider the differential diagnoses and associated pathologies, such as: (1) skin conditions: PV, prurigo nodularis, and bullous dermatosis; (2) drugs: selective serotonin and norepinephrine reuptake inhibitors, antiepileptics, potassium chloride, vitamin C, iron, magnesium, antiplatelets and anticoagulants (clopidogrel, dabigatran and rivaroxaban), nonsteroideal anti-inflamatory drugs (NSAIDS), aspirin, antibiotics (clindamycin), methotrexate and bisphosphonates; (3) physical, thermal, chemical or immunologic injury: hot beverages, caustic agents, alcohol, spicy food, repeat forceful vomiting, Mallory-Weiss syndrome, the rapid swallowing of large amounts of food, heavy smoking, oesophageal sclerotherapy or dilatation, mediastinal radiation, nasogastric intubation, coeliac disease or collagen vascular disorders. Additionally, impaired mobility and immunosuppression have also been implicated.

The late onset of EDS in the present case was unusual, because most of the time oesophageal involvement is simultaneously present with skin involvement. One possibility is that BP shifted to MMP. Although said condition has not been previously reported, our case leaves that possibility open. It is important to mention that although the clinical characteristics of MMP differ from those of BP, typified by the absence of mucosal membranes (MM) lesions, absence of predominant head-and-neck involvement, absence of scars, and older age at onset (>70 years), MMP and BP share pathophysiologic features. BP results from the activity of autoantibodies directed against BP230 and BP180, as with the majority of MMPs. However, the sera of most patients with BP react with the BP180-NC16A epitope, contrary to those of patients with MMP.¹

The prognosis of EDS associated with pemphigoid is favourable. Despite all the implications and the description of its various features, the direct mechanism of oesophageal damage remains unknown, and there are no specific diagnostic criteria for EDS. A misdiagnosis could lead to unnecessary investigation and treatment, so it is important to differentiate it from other entities and make a diagnosis of exclusion. A combination of acid suppression, discontinuation of precipitating medications and control of the causative disease results in complete healing.

Learning points.

• Pemphigus is a rare autoimmune disease that causes blistering of the skin and oral mucosa and can be related to esophagitis dissecans superficialis (EDS).

• EDS is a very rare benign, desquamative, chronic autoimmune disorder, with a self-limited process and a poorly understood pathogenesis.

• Endoscopic features of EDS are sloughing of large fragments of oesophageal mucosa lining, long linear mucosal break, vertical fissures, extensive bleeding and exudative esophagitis.

• Parakeratosis is the most frequent histologic finding in this pathology.

• EDS has been reported in association with skin conditions, drugs and physical, thermal, chemical or immunologic injury, as well as immunosuppression.