TMZ can help treat several conditions and types of tumors. Gliomas are tumors from glial cells in the brain and spinal cord, classified by the World Health Organization into grades I-IV. Grades III and IV, high-grade gliomas (HGG), are aggressive, with GBM, anaplastic astrocytoma, and anaplastic oligodendrocytoma being common. HGG has an annual incidence under 8 per 100,000, comprising about 1% of new cancers. TMZ treatment is well-tolerated, causing 5–10% hematological toxicity. It offers a favorable median survival of around 16 months [4].

Blepharoconjunctivitis is an ophthalmic condition that encompasses both blepharitis and conjunctivitis. This condition is characterized by inflammation occurring at both the eyelid margin and the surrounding conjunctiva. Various underlying causes have been associated with blepharoconjunctivitis, which is frequently multifactorial in nature. Of note, certain drug adverse reactions have also been associated as the culprit of this condition [10,11,12,13,14,15]. In the process of differential diagnosis, potential causes were carefully considered based on the patient’s history and physical examination. Allergic blepharoconjunctivitis, typically accompanied by itching, a rash, or a papillary reaction of the conjunctiva, was ruled out due to their absence. The possibility of an isolated eyelid dermatitis, characterized by skin changes on the eyelid without conjunctival involvement, was excluded based on the presence of a follicular reaction observed during the examination. This reaction aligns more closely with a pattern consistent with blepharoconjunctivitis rather than isolated dermatitis with a spill that caused irritation. However, it is accurate to note that the patient did exhibit both eyelid dermatitis and conjunctivitis. The immediate onset of symptoms following TMZ administration, the absence of systemic signs of infection, and the resolution of symptoms upon discontinuation of the drug, strongly suggests that the blepharoconjunctivitis in this case is more likely related to TMZ use rather than stemming from an infectious cause. Unfortunately, swabbing was not performed to further exclude viral blepharoconjunctivitis, which could have provided additional clarity in diagnosis.

There have been no reports thus far linking TMZ with the occurrence of blepharoconjunctivitis. However, other alkylating agents, such as cyclophosphamide, ifosfamide, and busulfan have been associated with blepharoconjunctivitis. Alkylating agents are known to cause dermatological adverse reactions due to their ability to damage DNA and disrupt cellular function. These agents chemically modify DNA molecules, leading to the formation of DNA adducts and cross-links. This DNA damage can trigger various cellular responses, including inflammation, apoptosis, and impaired cell replication. In the skin, alkylating agents can directly affect the rapidly dividing cells of the epidermis and hair follicles. This can lead to a range of dermatological adverse reactions, including rash, dryness and redness of the skin, and pruritus [5,6,7,8]. The underlying mechanism and cause of conjunctivitis in these cases are still unclear. The conjunctiva is composed of non-keratinized squamous epithelial cells and is relatively resistant to the cytotoxic effects of most chemotherapeutic agents, including alkylating agents. However, the inflammation associated with blepharitis can extend to involve the adjacent conjunctiva, leading to the development of blepharoconjunctivitis.

In our patient, TMZ is essential for managing GBM. Nevertheless, the initiation of the third TMZ cycle resulted in significant blepharoconjunctivitis. One might speculate that radiation dermatitis could be the cause of the periocular flareup. However, acute radiation-induced skin changes typically occur within days and peak within approximately two weeks [16]. In our case, these changes occurred abruptly more than one month after the last radiation dose. Establishing a cause-and-effect relationship between the use of TMZ and the abrupt appearance of blepharoconjunctivitis can be challenging due to the potential involvement of multiple causes for this eye condition. There could be other factors at play including confounding variables and the occurrence of unrelated events during that period.

Managing blepharoconjunctivitis encompasses a range of therapeutic approaches. The resolution of most cases has been demonstrated using topical and oral antibiotics, as well as topical steroids. Additionally, techniques such as warm lid compressions and eyelid hygiene have been reported to provide relief from blepharoconjunctivitis by promoting the stimulation of meibomian glands [17]. We elected to use topical steroid cream and eye drops for treatment in this case. Symptoms tremendously improved four days after initiating treatment.

In summary, this case report highlights a unique occurrence of blepharoconjunctivitis associated with the use of TMZ in a patient with glioblastoma grade IV. While TMZ is effective in treating glioblastoma, it can lead to ophthalmic side effects. Alkylating agents like TMZ have been known to cause dermatological adverse reactions due to their DNA-damaging properties, but specific reports linking TMZ with blepharoconjunctivitis are limited. This case underscores the importance of considering potential ophthalmic complications and implementing appropriate management strategies when administering alkylating agents.

The management of blepharoconjunctivitis involves various therapeutic approaches. Prompt treatment with topical steroid cream and eye drops resulted in significant symptom improvement in the reported case. However, further research is needed to better understand the mechanism and incidence of blepharoconjunctivitis associated with alkylating agents like TMZ. To establish a definitive cause, further investigations and well-controlled studies are necessary to rule out other potential contributors and demonstrate a consistent pattern of association. Healthcare providers should remain vigilant for potential ophthalmic side effects in patients undergoing treatment with these agents, ensuring comprehensive care to optimize treatment outcomes and patient well-being.