Chronic Insomnia as an Uncommon Manifestation of Celiac Disease: A Case Report

Introduction

Celiac disease (CD) is chronic, immune-mediated enteropathy triggered by the ingestion of gluten in genetically predisposed individuals. Its classical presentation comprising diarrhea, steatorrhea, weight loss, and malabsorption is well characterized.¹ However, it is now well recognized that celiac disease affects multiple organ systems beyond the gastrointestinal tract, including the nervous system, skin, musculoskeletal system, and reproductive system.² Indeed, extraintestinal manifestations may dominate the clinical picture, particularly in adults, rendering diagnosis challenging and often delayed.

The neuropsychiatric spectrum of celiac disease has received growing attention in recent decades. Manifestations including peripheral neuropathy, cerebellar ataxia, epilepsy, migraine, depression, anxiety, and cognitive dysfunction have been documented with increasing frequency.^3,4 The proposed pathophysiological mechanisms underlying these manifestations include direct immunological injury to neural tissue, micronutrient deficiencies (particularly of iron, folate, vitamin B12, and vitamin D), chronic systemic inflammation, and disruption of the gut-brain axis.^5,6

An additional, increasingly recognized mechanism is the presence of circulating anti-neuronal antibodies directed against the central and enteric nervous systems, which have been detected in a substantial proportion of patients with untreated celiac disease and neurological manifestations such as cerebellar ataxia, cognitive and memory/attention impairment, and peripheral neuropathy.⁷ Notably, sera from such patients have been shown to evoke neuronal injury through a mitochondrial-dependent apoptotic pathway in vitro, suggesting a potential direct pathogenic role for these antibodies in celiac-associated neurological impairment.⁸ Such findings lend support to a non-coincidental, immunologically mediated link between celiac disease and neurological dysfunction, of which sleep disturbance may plausibly form part.

Despite the expanding recognition of neuropsychiatric involvement in celiac disease, chronic insomnia as a predominant or presenting symptom is infrequently reported. A possible association between celiac disease and sleep disturbances, including insomnia, has been explored in observational studies, systematic reviews, and population-based analyses; however, sleep complaints in these reports are typically described as ancillary findings rather than the principal clinical concern.⁹ Importantly, insomnia is itself a highly prevalent and multifactorial symptom in the general population, arising from primary sleep disorders, psychiatric comorbidity, substance use, and lifestyle factors. This high baseline prevalence complicates the interpretation of any individual case and necessitates caution before attributing insomnia directly to celiac disease.

Herein, I report a case of chronic, treatment-resistant insomnia as the prodromal and predominant symptom of subsequently diagnosed celiac disease in a 42-year-old male patient. This report aims to highlight an uncommon clinical presentation, propose a neurological caveat for clinicians evaluating chronic insomnia, and advocate for multidisciplinary collaboration between neurology and gastroenterology in the workup of refractory sleep disturbances.

Herein, we report a case of chronic, treatment-resistant insomnia as the predominant symptom of subsequently diagnosed celiac disease in a 42-year-old male patient. This report aims to highlight an atypical clinical presentation, propose a diagnostic caveat for clinicians evaluating refractory chronic insomnia, and advocate for multidisciplinary collaboration between neurology and gastroenterology, while acknowledging that the high background prevalence of insomnia and the limitations inherent to a single case preclude firm conclusions regarding causality.

Case Presentation

History of Present Illness

A 42-year-old male patient presented to the outpatient neurology department at Baxnaano Hospital, Mogadishu, Somalia, with a chief complaint of persistent insomnia of five months’ duration. The patient described the insomnia as progressively worsening over the preceding months, with a profound impact on his occupational functioning, mood, and overall quality of life. He reported severe nocturnal restlessness characterized by an inability to both initiate and maintain sleep, lying awake for prolonged periods at bedtime, with frequent nocturnal awakenings and an inability to return to sleep thereafter. The resultant sleep deprivation caused marked daytime fatigue, impaired concentration, irritability, and significant psychological distress.

Prior to presentation, the patient had implemented various non-pharmacological interventions, including sleep hygiene techniques (maintaining a consistent sleep schedule, optimizing sleep environment, restricting caffeine intake, and limiting screen exposure before bedtime). He had also utilized over-the-counter sleep aids, including antihistamine-based preparations, without appreciable improvement. No prescription sedative-hypnotic medications had been trialed.

Past Medical, Surgical, and Family History

The patient’s past medical history was unremarkable for any previously diagnosed chronic medical conditions, psychiatric disorders, or surgical interventions. Family history was non-contributory, with no known history of autoimmune disorders, celiac disease, neurological conditions, or psychiatric illness among first-degree relatives.

Review of Systems and Dietary History

Upon detailed review of systems, the patient endorsed chronic but mild abdominal distension and vague abdominal discomfort, which he had experienced for several years. These symptoms had been mild and intermittent in nature, and the patient had adapted to them over time without seeking formal medical evaluation. He denied overt diarrhea, steatorrhea, significant weight loss, oral ulceration, skin rashes, joint pains, or symptoms suggestive of thyroid dysfunction.

Notably, dietary history revealed that the patient’s daily meals consisted almost exclusively of wheat-based products, a common dietary pattern in the local cultural and socioeconomic context. This finding was considered clinically significant in the context of the presenting symptoms.

Physical Examination

On general examination, the patient appeared fatigued but was alert, oriented, and cooperative. Vital signs were within normal limits (blood pressure, heart rate, temperature, and respiratory rate were all unremarkable). Body mass index was within the normal range.

Neurological Examination

A comprehensive neurological examination was performed. Cranial nerve testing was intact bilaterally. Motor examination revealed normal tone, bulk, and strength (5/5) in all four extremities. Sensory examination was normal to light touch, pinprick, vibration, and proprioception. Deep tendon reflexes were symmetric and normoactive. Cerebellar testing (finger-to-nose, heel-to-shin, rapid alternating movements) was performed without dysmetria or dysdiadochokinesia. Gait was normal, including tandem gait. There were no signs of meningeal irritation.

Abdominal Examination

Trivial abdominal distension was noted on inspection. Bowel sounds were present and normal. Palpation revealed no tenderness, masses, or organomegaly.

Serological Testing

A Polycheck Celiac IgG panel was performed. The results are shown in Table 1.

Table 1 Celiac disease serology results (IgG-based testing)

The borderline elevation in tTG IgG, while not strongly positive, was considered significant in the clinical context and warranted further investigation. It should be noted that IgG-based antibody assays may have lower sensitivity and specificity compared to IgA-based celiac serology, and borderline values in the appropriate clinical setting should not preclude further diagnostic evaluation.¹⁰

Upper Gastrointestinal Endoscopy

Upper gastrointestinal endoscopy was performed by the consulting gastroenterologist. The esophagus, stomach, and pylorus demonstrated normal mucosa with no erosions, ulceration, varices, or masses. However, the first and second portions of the duodenum (D1 and D2) demonstrated erythematous and edematous mucosa, a finding suspicious for celiac disease (Figure 1). Multiple mucosal biopsies were obtained from the duodenal segments for histopathological examination.

Figure 1 Upper gastrointestinal endoscopy report demonstrates erythematous and edematous mucosa in the first (D1) and second (D2) portions of the duodenum, with multiple biopsies obtained for histopathological analysis.

Histopathological Examination

Histopathological analysis of the duodenal biopsies revealed partial (mild) villous atrophy with reduction in villous height-to-crypt depth ratio, crypt hyperplasia with elongation and increased mitotic activity, surface enterocyte flattening with loss of normal columnar morphology, and increased intraepithelial lymphocytes (42 IEL per 100 enterocytes; normal ≤25 IEL/100 enterocytes). These histological features were consistent with Marsh-Oberhuber classification type 3a (infiltrative-hyperplastic lesion with partial villous atrophy), a well-established histopathological pattern diagnostic of celiac disease¹¹ (Figure 2).

Figure 2 Photomicrographs showing duodenal mucosa with (A) mild villous atrophy, increased intraepithelial lymphocytes, and crypt hyperplasia (H&E, x10) and (B) a magnified view of the increased intraepithelial lymphocytes (H&E, x20).

Diagnosis

Based on the integration of clinical presentation, serological findings (borderline tTG IgG elevation), endoscopic findings (erythematous and edematous duodenal mucosa), and confirmatory histopathological evidence (Marsh-Oberhuber type 3a changes), a definitive diagnosis of celiac disease was established.

Treatment and Outcome

Following the diagnosis, the patient commenced on a strict, lifelong gluten-free diet (GFD) with comprehensive dietary counseling. The patient was educated regarding the identification and avoidance of gluten-containing foods and the potential for cross-contamination.

Clinical Response

The patient demonstrated a dramatic and clinically significant improvement in both insomnia and gastrointestinal symptoms within weeks of initiating the GFD. Specifically, the patient reported: Restoration of normal sleep initiation latency, consolidated and restorative nocturnal sleep, resolution of nocturnal restlessness, marked improvement in daytime alertness, mood, and concentration and resolution of abdominal distension and discomfort.

The temporal correlation between the institution of the gluten-free diet and the resolution of insomnia is suggestive of a possible association between celiac disease and the patient’s sleep disturbance, although, in the absence of objective sleep assessment and given the high background prevalence of insomnia, a direct causal relationship cannot be established.

Discussion

This case illustrates the clinical subtlety and diagnostic complexity inherent in atypical presentations of celiac disease. While the classical triad of diarrhea, malabsorption, and weight loss remains the most widely recognized manifestation, the present case underscores that extraintestinal symptoms may dominate the clinical picture and constitute the presenting complaint, particularly in adult patients.

The neuropsychiatric spectrum of celiac disease has been the subject of increasing scientific interest. Hadjivassiliou, Sanders, Grünewald, Woodroofe, Boscolo and Aeschlimann³ provided seminal evidence that gluten sensitivity can manifest with a wide array of neurological disorders, including cerebellar ataxia, peripheral neuropathy, and encephalopathy, even in the absence of significant gastrointestinal involvement. Subsequent studies have expanded this spectrum to include depression, anxiety, cognitive impairment (“brain fog”), and, less commonly, sleep disturbances.⁴

Several plausible pathophysiological mechanisms may underline the association between celiac disease and insomnia. Immune-mediated neuroinflammation represents a key pathway, as celiac disease is characterized by systemic immune activation with elevated levels of pro-inflammatory cytokines that can traverse the blood-brain barrier and disrupt sleep-regulating neural circuits in the hypothalamus and brainstem.¹² Additionally, malabsorption in celiac disease frequently leads to micronutrient deficiencies in iron, folate, vitamin B12, vitamin D, and magnesium, all of which have documented roles in sleep regulation; iron deficiency, in particular, has been implicated in restless legs syndrome and insomnia through its role in dopaminergic neurotransmission.¹³ Gut-brain axis disruption constitutes another important mechanism, as the bidirectional communication between the gastrointestinal tract and the central nervous system is increasingly recognized as a critical modulator of mood, cognition, and sleep, and intestinal inflammation and dysbiosis associated with celiac disease may perturb this axis, contributing to sleep disturbance.¹⁴ Furthermore, serotonin dysregulation may play a role, given that approximately 95% of the body’s serotonin is synthesized in the gut; intestinal mucosal inflammation in celiac disease may impair serotonin synthesis and metabolism, consequently affecting central serotonergic pathways that are integral to sleep-wake cycle regulation.¹⁵

The borderline tTG IgG result in this case highlights the limitations of relying exclusively on serological markers for diagnosis. IgA-based assays (tTG IgA and endomysial antibodies) are preferred for their higher sensitivity and specificity; however, in settings where IgA deficiency is present or IgA-based assays are unavailable, IgG-based panels may be utilized, with the understanding that borderline results in an appropriate clinical context warrant endoscopic evaluation.¹⁶ The gold standard for celiac disease diagnosis remains duodenal biopsy with histopathological assessment according to the Marsh-Oberhuber classification. In this case, the identification of Marsh 3a changes provided definitive confirmation.¹¹ The patient’s wheat-dominant diet reflective of local dietary customs was a critical diagnostic clue. In populations where wheat constitutes a dietary staple, the prevalence of celiac disease may be underestimated, and clinicians should maintain heightened awareness.¹⁷

The resolution of insomnia following the institution of a gluten-free diet in this patient provides anecdotal support for a possible association between celiac disease and sleep disturbance, though it does not constitute proof of causation. This temporal association is consistent with prior reports of improvement in neuropsychiatric symptoms following dietary intervention in celiac disease.¹⁸

While this observation alone does not establish causality, it contributes to the growing body of evidence supporting the role of gluten-mediated immune activation in the pathogenesis of sleep disturbance.

This case serves as a clinical caveat for neurologists and sleep medicine specialists: celiac disease should be included in the differential diagnosis of chronic, unexplained insomnia, particularly in patients who present with insomnia that is refractory to conventional pharmacological and behavioral interventions, coexistent subtle or non-specific gastrointestinal symptoms such as abdominal distension, bloating, or vague discomfort, dietary patterns characterized by high gluten intake, unexplained micronutrient deficiencies in iron, folate, vitamin B12, or vitamin D, a personal or family history of autoimmune disorders, or the presence of other unexplained neuropsychiatric symptoms including fatigue, cognitive impairment, and mood disturbance. Early recognition and timely diagnosis of celiac disease in such presentations can significantly enhance patient quality of life and prevent the long-term sequelae of untreated disease, including osteoporosis, infertility, and an increased risk of lymphoproliferative malignancies.¹

There is several methodological limitations regarding this case in which the association between celiac disease and insomnia has been examined in prior observational studies, systematic reviews, and population-based analyses without establishing direct causality, so this single case represents an additional clinical observation rather than confirmatory evidence. Insomnia is also a highly prevalent, multifactorial symptom, and its co-occurrence with celiac disease may be coincidental. Importantly, insomnia was assessed clinically without objective sleep measurement (eg, polysomnography or actigraphy) or validated rating scales, no detailed psychiatric evaluation was performed, and anxiety, depression, and other primary sleep disorders were not formally excluded The improvement following a gluten-free diet, while temporally associated, could also reflect natural symptom fluctuation, placebo effects, or concurrent lifestyle changes. The relationship described here should therefore be interpreted as a possible, temporally associated finding rather than a confirmed causal one, and prospective studies using objective sleep assessment and standardized psychiatric evaluation are needed.

Conclusion

Celiac disease is a multisystem autoimmune disorder whose clinical spectrum extends far beyond the gastrointestinal tract. This case demonstrates that chronic insomnia may represent an atypical yet clinically significant extraintestinal manifestation of celiac disease. The resolution of insomnia following the adoption of a gluten-free diet in this patient supports a possible association and the therapeutic potential of dietary intervention; however, given the absence of objective sleep assessment and the high prevalence of insomnia in the general population, this observation should be regarded as suggestive rather than confirmatory of causality.

Celiac disease should be considered, particularly in the presence of subtle gastrointestinal symptoms, high dietary gluten intake, or unexplained micronutrient deficiencies. Interdisciplinary collaboration between neurology and gastroenterology is essential for the timely recognition, diagnosis, and management of such presentations, ultimately leading to optimal patient outcomes.