Illustration of methotrexate side effects mimicking Behcet's Disease

Is That Really Behçet's? When Common Medications Mimic Rare Diseases

Soraya Malik in Health & Wellness December 2025 • 4 min read.

"A Case Study: How Methotrexate Side Effects Can Resemble Behçet's Disease, Leading to Diagnostic Confusion"

Methotrexate (MTX) is a medication widely used to treat various conditions, including psoriasis, rheumatoid arthritis, and certain types of cancer. It works by interfering with DNA synthesis, which helps to slow down the growth of rapidly dividing cells. This makes it effective in managing autoimmune diseases where the body's immune system attacks its own tissues.

Like all medications, MTX can cause side effects. While many are well-documented—such as nausea, fatigue, and hair loss—some are less common and can even mimic the symptoms of other diseases. This can lead to confusion and potentially delay the correct diagnosis. This case study sheds light on one such instance, where MTX side effects closely resembled Behçet's disease.

Behçet's disease is a rare and complex condition characterized by inflammation of blood vessels throughout the body. This can lead to a variety of symptoms, including mouth sores, genital sores, eye inflammation (uveitis), and skin lesions. Because these symptoms can also occur in other conditions, diagnosing Behçet's disease can be challenging.

The Case: MTX Side Effects Mimicking Behçet's Disease

Illustration of methotrexate side effects mimicking Behcet's Disease

A 63-year-old woman with a history of necrotizing scleritis (a severe inflammatory condition affecting the eye) was being treated with methotrexate. Shortly after starting the medication, she developed several alarming symptoms: painful ulcers in her mouth and genital area, and purplish, crusted patches on her legs. These symptoms bore a striking resemblance to Behçet's disease, prompting her doctors to investigate further.

The diagnostic process involved a thorough examination and several tests to differentiate between Behçet's disease and potential MTX side effects. Here's a breakdown of the key steps:

Symptom Evaluation: Doctors carefully assessed the specific symptoms, noting the presence and characteristics of the ulcers and skin lesions.
Laboratory Tests: Blood tests were conducted to look for markers of inflammation, immune system activity, and potential causes of the symptoms. Notably, the patient tested positive for HLA-B51, a genetic marker associated with Behçet's disease. However, other tests, such as the pathergy test (a skin reactivity test), were negative.
Histopathology: A biopsy of the skin lesions was performed to examine the tissue under a microscope. The results showed some features suggestive of drug-induced reactions but lacked the specific signs of vasculitis (blood vessel inflammation) typically seen in Behçet's disease.
Medication Review: Doctors carefully reviewed the patient's medication list and considered the possibility that MTX could be causing the symptoms.

Considering the timeline of symptom onset in relation to the MTX treatment, along with the lab results and histopathology findings, the doctors concluded that the patient's symptoms were likely a side effect of methotrexate rather than true Behçet's disease. The MTX was discontinued, and the patient was started on alternative treatments, including pyridoxine (vitamin B6). Gradually, the ulcers and skin lesions healed completely, and there was no recurrence after 12 months.

Key Takeaways: What This Case Means for You

This case highlights the importance of recognizing that medications can sometimes cause unexpected side effects that mimic other diseases. While this particular scenario is rare, it underscores the need for careful monitoring of patients on MTX and other drugs with the potential for unusual reactions. Open communication between patients and their healthcare providers is essential for early detection and appropriate management of any adverse effects. If you're experiencing new or worsening symptoms while taking MTX, don't hesitate to discuss them with your doctor.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.5021/ad.2011.23.3.412, Alternate LINK

Title: A Case Of Cutaneous Side Effect Of Methotrexate Mimicking Behçet'S Disease

Subject: Dermatology

Journal: Annals of Dermatology

Publisher: Korean Dermatological Association and The Korean Society for Investigative Dermatology

Authors: Hyun Jae Lee, Soon Kwon Hong, Jong Keun Seo, Deborah Lee, Ho Suk Sung

Published: 2011-01-01

Everything You Need To Know

What is methotrexate, and why is it used?

Methotrexate (MTX) is a drug used to treat autoimmune diseases like psoriasis and rheumatoid arthritis, as well as certain cancers. It functions by disrupting DNA synthesis, which slows the growth of rapidly dividing cells. This is significant because it helps manage conditions where the body's immune system mistakenly attacks its own tissues, reducing inflammation and cell proliferation. However, it's important to be aware that methotrexate can have side effects, some of which can resemble other diseases, potentially leading to diagnostic challenges.

What is Behçet's disease, and why is it so difficult to diagnose?

Behçet's disease is a rare and complex disorder characterized by the inflammation of blood vessels throughout the body. This inflammation can cause a variety of symptoms, including painful mouth and genital sores, eye inflammation known as uveitis, and skin lesions. Diagnosing Behçet's disease can be difficult because these symptoms are not unique to this condition and can occur in other diseases as well. Genetic markers, such as HLA-B51, can be associated with Behçet's disease, but their presence alone isn't definitive.

How do doctors determine whether symptoms are caused by methotrexate side effects or by a condition like Behçet's disease?

The process of distinguishing between methotrexate (MTX) side effects and conditions like Behçet's disease involves several key steps. Doctors typically perform a thorough symptom evaluation, looking closely at the specific characteristics of ulcers and skin lesions. Laboratory tests, including blood work, are conducted to identify markers of inflammation and immune system activity. A histopathology, or biopsy of skin lesions, may be performed to examine the tissue for signs of vasculitis, which is common in Behçet's disease but not always present in MTX side effects. A careful medication review is also essential to assess the likelihood that MTX is causing the symptoms.

What is HLA-B51, and what does it mean if someone tests positive for it?

HLA-B51 is a genetic marker that is often associated with Behçet's disease. The presence of HLA-B51 can increase the likelihood of a Behçet's diagnosis; however, it is not definitive. Many people with the gene never develop the condition, and others can have Behçet's disease without having the gene. Therefore, while a positive HLA-B51 test can raise suspicion for Behçet's disease, doctors must consider it in conjunction with clinical symptoms and other diagnostic findings.

What is necrotizing scleritis, and why is it important in this context?

Necrotizing scleritis is a severe inflammatory condition that affects the eye. It causes inflammation and damage to the sclera, which is the white outer layer of the eyeball. It's significant because it can lead to severe eye pain, vision loss, and even loss of the eye if not treated promptly and effectively. Given its severity, managing necrotizing scleritis often requires strong immunosuppressant medications like methotrexate to control the inflammation and prevent further damage. However, as illustrated, medications can present diagnostic challenges due to potential side effects.