G&H What are the underlying etiologies of dermatologic conditions that can involve the esophagus?
DK The underlying etiologies can be divided into several categories. The first is autoimmune, which is comprised of disorders such as lichen planus and pemphigoid disease. The second includes inherited disorders such as epidermolysis bullosa dystrophica and tylosis. The third category consists of an infectious disorder that occurs in immunocompromised patients termed mucosal candidiasis (Figure 1). Notably, some dermatologic disorders can be associated with other diseases, such as lichen planus with hepatitis C infection and pemphigoid with malignancy. For these skin disorders, gastroenterologists need to check for associated underlying disorders as well.
G&H What are the characteristic clinical and endoscopic features of these conditions?
DK It depends on the condition. For example, lichen planus, as shown in Figure 2, commonly has a white or lacy, almost blanched appearance. There will be sloughing on biopsy, and strictures are very common with lichen planus. Sometimes, lichen planus can lead to scarring, manifesting as ring formation, almost like that seen in patients with eosinophilic esophagitis; however, this type of ring formation can be typical of any scarring process.
For the other disorders such as tylosis and pemphigus, the esophageal mucosa may appear completely normal on endoscopy. This makes it difficult sometimes to differentiate dermatologic disorders from other causes of strictures. However, with the exception of pemphigus and epidermolysis bullosa dystrophica, there is often severe sloughing with biopsies. The gastroenterologist must be careful, as a matter of fact, with pemphigus and epidermolysis because the process of obtaining biopsies can create a stricture. Part of the importance of discussing this topic is to highlight how necessary it is to keep dermatologic disorders in mind. Often, the diagnosis is not so obvious, when taking into account the bland endoscopic appearance.
G&H Does disease activity in skin mirror that in the esophagus?
DK This is a very important question. For most of these diseases, the answer is generally yes, yet for even some of the rarer diseases such as pemphigus, the condition may present with initial esophageal involvement. Epidermolysis bullosa dystrophica is diagnosed in infancy by its skin manifestations and is easily recognizable before esophageal involvement. Tylosis usually presents in teenage years with the classic hypertrophic skin on the palms and soles of the feet before esophageal involvement. The one exception is lichen planus, where patients may present with dysphagia as their initial symptom. At that point, one has to determine whether lichen planus is truly a primary disorder of the esophagus or whether there are subtle signs of extraesophageal lichen planus (such as in the mouth or in the genital area) that did not come to clinical attention or were missed on examination.
G&H How common are esophageal dermatoses?
DK Most of these are rare, particularly the inherited disorders. Again, the one exception is lichen planus. Although previously thought to be rare, lichen planus may be more common than realized. This is likely because many patients with lichen planus have had esophageal dilations over the years, strictures of unclear etiology, and until later on, it is not often determined that lichen planus was originally underscored. In my practice, when I see a middle-to-older-age woman with a proximal stricture, lichen planus is almost always the cause. Certainly, compared with reflux disease or eosinophilic esophagitis, lichen planus as a cause of stricture is rare; however, lichen planus is much more common than has been appreciated in the past.
G&H What are the challenges in diagnosing esophageal dermatoses?
DK There are several challenges. The first is to think about them. Given their rare status, esophageal dermatoses will come to the gastroenterologist’s attention only a few times a year. They will not be at the top of the list when evaluating an abnormal appearance of the esophagus or stricture, but it is important to keep them in mind. The second is that endoscopic findings are often not specific in presentation; the only finding seen may be a bland stricture. Other classic signs should be sought, such as sloughing or endoscopic Nikolsky sign with pemphigus. The third challenge is that similar to endoscopy, classic findings on biopsy such as Civatte bodies in lichen planus or specific antibodies sought on dermatopathology, although helpful, are often not present. Gastroenterologists may hesitate to diagnose a skin disorder unless the pathologist says that it clearly is one. The diagnosis of many skin disorders involving the esophagus is not based on just a biopsy finding but is often made by combining the clinical presentation, endoscopic signs, and some of the nonspecific biopsy findings. The combination of these provides much more evidence that a skin disease may be present and affecting the esophagus.
G&H When should esophageal lichen planus be considered?
DK Clinicians always used to consider lichen planus as a finding, as I mentioned, of a proximal esophageal stricture in a woman with a history of genital or, even more likely, oral lichen planus. This still stands; however, it is now known that isolated esophageal lichen planus occurs, that it can occur in any part of the esophagus, and men can be affected as well. A typical history I see in my practice is one of patients who have had numerous dilations of an esophageal stricture with rapid recurrence (sometimes even stent placement) and lack of response to proton pump inhibitors, as well as nonspecific biopsy findings, and there has not been enough grounds in the eyes of the gastroenterologist to make the diagnosis of lichen planus. The diagnosis can be suspected endoscopically by some of the characteristic findings I mentioned, such as sloughing with a biopsy and a white lacy appearance of the mucosa. The key is that when a patient has a recurrent stricture and no other etiology can be found to explain why this stricture keeps recurring and does not respond well to dilation, lichen planus should be high on the differential diagnosis.
G&H Which esophageal dermatoses are premalignant and require surveillance?
DK It is difficult to perform broad epidemiologic studies to answer this question, given the rarity of esophageal dermatoses. However, my colleagues and I performed a systematic analysis, demonstrating that the incidence of cancer in lichen planus is about 100 times more than in the rest of the population. I bring these patients back every 2 or 3 years for surveillance. Indeed, some patients may present with de novo squamous cell cancer and lichen planus. It is important to be aware of the occurrence of cancer in these patients, not only as far as developing over time, but at the initial diagnosis, when multiple biopsies need to be taken. Tylosis carries up to a 95% risk of esophageal squamous carcinoma by age 65 years, and affected patients require surveillance starting at age 20 years. Epidermolysis bullosa dystrophica has also been reported with cancer. However, gastroenterologists must be careful because performing biopsies in these patients, as in any form of trauma to the esophageal mucosa in this disease, may cause scarring and stricture formation. For this reason, surveillance in these patients is more controversial. However, I will start surveillance of these patients when they are in their 20s and will continue it every couple of years.
G&H For the gastroenterologist, how should a dermatosis with esophageal involvement be managed?
DK Most importantly, gastroenterologists have to manage a dermatosis with esophageal involvement in conjunction with a dermatologist. The dermatologist will know much more about these diseases than a gastroenterologist will, particularly when considering systemic therapies. A dermatologist will be more familiar and more confident with applying drugs such as systemic corticosteroids, rituximab, and other immunosuppressants when it comes to these dermatologic conditions. Gastroenterologists can administer topical corticosteroids similar to the management of patients with eosinophilic esophagitis. At least in case series, this treatment may be helpful for patients with lichen planus. The use of corticosteroids and other topical therapies, such as tacrolimus, in other autoimmune skin disorders has been tried and is likely worth trying, although the data for these therapies are only through case series, so not as strong. However, often, these patients have few therapeutic options other than systemic therapy, so it is something we will try.
G&H In what areas is further research needed?
DK We need to understand better why some patients with systemic dermatoses develop esophageal involvement while others do not. Most importantly, better endoscopic and histologic markers are needed to make a definitive diagnosis for these disorders, as many are left untreated for years because of lack of diagnosis. Education of gastroenterologists is key because, as I mentioned, many of these disorders, particularly lichen planus, remain undiagnosed for years. Esophageal dermatoses are not thought about, or they do not have a classic presentation, and as a result, many patients could suffer, when perhaps much earlier on in their disease course, they can be effectively treated and dysphagia well controlled.
Disclosures
Dr Katzka has no relevant conflicts of interest to disclose.
Suggested Reading
Aby ES, Eckmann JD, Abimansour J, et al. Esophageal lichen planus: a descriptive multicenter report. J Clin Gastroenterol. 2024;58(5):427-431.
Arar AM, DeLay K, Leiman DA, Menard-Katcher P. Esophageal manifestations of dermatological diseases, diagnosis and management. Curr Treat Options Gastroenterol. 2022;20(4):513-528.
Camilleri MJ. Cutaneous diseases of the esophagus. In: Richter JE, Castell DO, Katzka DA, et al, eds. The Esophagus. 6th ed. New York, NY: John Wiley & Sons Ltd; 2021:chap 46.
Kamboj AK, Gibbens YY, Hagen CE, Wang KK, Iyer PG, Katzka DA. Esophageal epidermoid metaplasia: clinical characteristics and risk of esophageal squamous neoplasia. Am J Gastroenterol. 2021;116(7):1533-1536.
Katzka DA, Smyrk TC, Bruce AJ, Romero Y, Alexander JA, Murray JA. Variations in presentations of esophageal involvement in lichen planus. Clin Gastroenterol Hepatol. 2010;8(9):777-782.
Podboy A, Sunjaya D, Smyrk TC, et al. Oesophageal lichen planus: the efficacy of topical steroid-based therapies. Aliment Pharmacol Ther. 2017;45(2):310-318.
Pomenti SF, Flashner SP, Del Portillo A, et al. Clinical and biological perspectives on noncanonical esophageal squamous cell carcinoma in rare subtypes. Am J Gastroenterol. 2024;119(12):2376-2388.
Ravi K, Codipilly DC, Sunjaya D, Fang H, Arora AS, Katzka DA. Esophageal lichen planus is associated with a significant increase in risk of squamous cell carcinoma. Clin Gastroenterol Hepatol. 2019;17(9):1902-1903.e1.
Reddy CA, McGowan E, Yadlapati R, Peterson K. AGA clinical practice update on esophageal dysfunction due to disordered immunity and infection: expert review. Clin Gastroenterol Hepatol. 2024;22(12):2378-2387.