The report, authored by Walid Alesefir of the Internal Medicine Department at Hail University in Saudi Arabia, describes a 41-year-old Pakistani man employed in a high-stress office job who had endured recurrent headaches for approximately 21 years. His attacks were classic in many respects: bilateral pressure-like pain centered on the frontal and supra-orbital regions, striking two to three times per month and lasting from several hours to occasionally days, accompanied by photophobia, phonophobia, and nausea. Psychological stress and sunlight exposure were his main triggers, and he typically retreated to a dark room with an over-the-counter combination of acetaminophen, caffeine, and codeine.

What set his case apart was the skin. For many years, his attacks had been accompanied by recurrent, non-palpable, non-pruritic erythematous changes over the bilateral forehead, and the distribution of these red patches corresponded approximately to the ophthalmic, or V1, territory of the trigeminal nerve, broadly mirroring the bilateral frontal and supra-orbital distribution of his headache itself. The lesions were well-demarcated and appeared with reproducible timing across attack after attack. Following his usual acute treatment, improvement in both the headache and the forehead erythema occurred within minutes to a few hours, with the cutaneous changes generally resolving in parallel with the pain, a detail that the author considers strong supportive evidence of a close temporal association between the two phenomena.

Because the symptoms had spanned more than two decades, the patient could not reliably recall whether the migraine-type headaches had preceded the cutaneous manifestations or whether the two had been intertwined from the very beginning. He also experienced intermittent cranial autonomic features during some attacks, such as the lacrimation, nasal congestion, and facial sweating that are classically associated with trigeminal autonomic cephalalgias like cluster headache but are known to occur in migraine as well. Intriguingly, these conventional autonomic symptoms were not consistently present and did not invariably coincide with the forehead discoloration, a distinction that the report argues should caution clinicians against simply assuming that the visible redness represents an ordinary cranial autonomic symptom.

The diagnostic workup was thorough and, crucially, unremarkable. The patient was afebrile with normal vital signs, a body mass index of 25.17 kilograms per square meter, and a completely normal neurological examination covering mental status, cranial nerves, motor and sensory function, coordination, and gait. Laboratory evaluation, including complete blood count, renal function tests, inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein, and vitamin B12, all fell within normal limits. Brain MRI without contrast showed preserved gray-white matter differentiation and no evidence of infarction, hemorrhage, mass lesion, hydrocephalus, mesial temporal sclerosis, cortical dysplasia, or focal brainstem or cerebellar lesion. His only notable medical history was lumbar disc disease, and although he reported a positive family history of migraine in first-degree relatives, there was no family history of similar headache-associated skin lesions.

The biological explanation, while still uncertain, points toward some of the most intensively studied machinery in modern neuroscience. Migraine is now understood as a complex neurobiological disorder involving cortical, brainstem, and trigeminovascular networks, in which activation of trigeminal afferents promotes the release of vasoactive neuropeptides, most notably calcitonin gene-related peptide, or CGRP, driving vasodilation and neurogenic inflammatory signaling. Because the trigeminal nerve’s ophthalmic branch supplies the forehead, activation of this pathway offers a plausible route by which a migraine attack could produce visible vascular change in the overlying skin. Previous reports of migraine-associated forehead erythema have proposed extracerebral vasodilation, trigeminovascular activation, autonomic dysfunction, and neurogenic inflammation as candidate mechanisms.

Some of the strongest hints come from histopathology. In one previously published case, biopsy of the erythematous forehead lesions demonstrated perivascular dermatitis, extravasated erythrocytes, endothelial swelling, and fibrinoid material in vessel walls, findings that support the possibility that genuine vascular change coexists with local inflammatory processes during attacks. The report also highlights an intriguing therapeutic opportunity: the availability of gepants, a class of CGRP receptor antagonists, means that in similar patients, prospectively documenting whether acute treatment with a gepant produces parallel improvement in both the migraine attack and the erythematous lesion could provide functional evidence for CGRP-related trigeminovascular involvement. Such a response, the author stresses, would remain hypothesis-generating and would not by itself establish causality.

The new case joins a remarkably small published literature. Sethi and colleagues first described the classic red forehead dot syndrome in 2007, in a 40-year-old man with episodic migraine whose red forehead dot extended toward the periorbital V1 region and, in some severe attacks, was accompanied by sweating. A 2015 teaching neuroimage revisited the phenomenon in a 32-year-old woman with a red forehead dot and eyelid ecchymosis in the V1 distribution, with normal MRI, magnetic resonance angiography, and venography. Berdouk and Khan reported a 28-year-old Pakistani man whose multiple linear erythematous markings over the forehead and nose darkened with greater headache severity and resolved after the migraine. Durmaz and Demirkesen described a 36-year-old man with ovoid and triangular erythematous, telangiectatic macules on the forehead and hairline during severe attacks, while Muhammad and colleagues reported two Pakistani women, one with linear erythematous streaks and the other with multiple discoid erythematous patches with edema, both concurrent with migraine and resolving after improvement.

What emerges from this scattered literature is striking heterogeneity in morphology and timing. Some patients develop a single localized dot, others linear markings, patches, or ecchymotic changes, and in several reports the intensity of the skin findings tracked with headache severity. Yet the common thread is a reproducible temporal relationship with migraine attacks and resolution as the headache subsides, together with consistently normal imaging and laboratory evaluations. The present case is notable for its long duration, its bilateral and well-demarcated presentation, and the parallel improvement of pain and erythema within minutes to a few hours after usual acute therapy, adding a distinctive entry to this rare phenotypic spectrum.

The report is candid about its limitations: it describes a single patient, the chronology depends on long-term recall, no active lesion was present during the clinic assessment, and objective dermatological or vascular assessment during an attack was not performed. For clinicians, the practical message is twofold. Unusual cutaneous findings accompanying headache, particularly at first presentation, warrant careful evaluation to exclude secondary neurological, vascular, inflammatory, and dermatological causes according to the clinical context and the presence of red flags. But once relevant alternatives have been excluded, recognition of a stable, recurrent, tightly headache-associated pattern may help avoid unnecessary repeated investigations and provide reassurance to patients. As research into CGRP and the trigeminovascular system continues to reshape migraine therapy, this rare red mark on the forehead may yet prove to be one of the most revealing windows into the biology of the world’s most disabling neurological disorder.

Subject of Research: A rare case report documents bilateral forehead erythema appearing in sync with migraine attacks, shedding light on the trigeminovascular mechanisms behind red forehead dot syndrome.

Article Title: Red forehead dot syndrome: a case report and review of literature

Article References: Alesefir, W. (2026). Red forehead dot syndrome: a case report and review of literature. Frontiers in Pain Research, 7, Article 1888803. https://doi.org/10.3389/fpain.2026.1888803

Image Credits: AI Generated

DOI: 10.3389/fpain.2026.1888803

Keywords: migraine, red forehead dot syndrome, CGRP, trigeminal nerve, neurogenic inflammation, headache, case report, forehead, syndrome, case, report, review