Co-Occurrence of Systemic Sclerosis, Lupus, and Celiac Disease in Multiple Autoimmune Syndrome: A Case Report

Introduction

Multiple autoimmune syndromes (MAS) are described as the coexistence of more than 2 autoimmune disorders. MAS are due to the underlying immune dysregulation pathways and shared genetic polymorphisms that make the overlap more likely.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are connective tissue diseases that do not overlap commonly, due to the underlying pathogenesis and antibody profile. While the pathogenesis of SSc is highlighted by small vessel vasculopathy and fibroblast dysfunction that results in organ fibrosis along with autoantibody synthesis [1], tissue injury due to SLE is induced by complex interactions between genetic, epigenetics, environmental, and immune systems. The immune system involvement in SLE includes innate and adaptive immunity, with resultant autoantibody production and cytokine cascades [2]. Celiac disease (CD) is one of the most prevalent causes of malabsorption. It is an immune-mediated small intestine pathology that alters the small intestine’s ability to absorb nutrients adequately [3,4].

The coexistence of SLE and CD has been reported previously in several case reports [3,5,6], as has the coexistence of SSc and CD [7,8] and SSc and SLE, which is usually referred to as overlap syndrome [9]. We report a patient with a unique presentation of SLE, CD, and SSc. The coexistence of these 3 conditions, SLE, SSC and CD, is important to highlight, as their clinical presentations can overlap, potentially leading to missed diagnoses. Therefore, it is essential to consider investigating other autoimmune syndromes as clinically indicated.

Case Report

A 21-year-old woman was known to have juvenile SSc and interstitial lung disease since 2014. She was admitted to our hospital with a 5-day history of upper respiratory tract infection that started with mild productive cough with whitish sputum. After 3 days, she started to develop subjective fever. She also reported unchanged long-standing mild, dull, episodic lower abdominal pain and diarrhea associated with unintentional weight loss of 4 kg over the previous 3 months. There was no blood or mucus in the stool. In addition, she had a long-standing history of dysphagia related to underlying SSc, which was not noted to be worsening. On examination, her vital signs were stable. Her weight was 31 kg, and her body mass index was 14.7 kg/m2.

The patient had sclerodactyly in both hands with fifth finger deformity bilaterally and bilateral fifth proximal interphalangeal joint tenderness (Figure 1A, 1B). No vitiligo or rash was observed on general inspection. There were bilateral basal inspiratory crackles, matching her baseline. Abdominal examination revealed mild lower quadrant abdominal tenderness.

Laboratory investigations revealed significant leukopenia (WBC 1.9×109/L) with an absolute lymphocyte count of 0.4/μL, along with normocytic normochromic anemia (hemoglobin level of 84 g/L), thrombocytopenia (platelet count of 115), and an erythrocyte sedimentation rate of 16 mm/h. Liver and kidney function test results were unremarkable. The peripheral blood smear result was also unremarkable. Virology screening, including HIV, was negative. Chest X-ray showed new left lower zone alveolar opacity associated with air bronchogram, in the context of decreased lung volume bilaterally and mild bilateral basal interstitial opacities.

The patient was treated for community-acquired pneumonia, which resulted in an improvement of her respiratory status. However, she continued to have persistent pancytopenia. Subsequently, autoimmune panel came back positive for antinuclear antibody, at 1: 10240 (fine speckled pattern), with positive anti-double-stranded DNA of 677 IU/mL and low complement, C3 and C4. SLE was diagnosed based on positive serology, along with the presence of pancytopenia, and the patient was started on a steroid and hydroxychloroquine.

The patient underwent upper gastrointestinal endoscopy for further evaluation of chronic diarrhea, which showed scalloping and fissuring of the duodenal part (Figure 2). Biopsy from the endoscopy revealed intraepithelial lymphocytic infiltration and villous atrophy, which led to the request for Celiac serology, which came back positive for anti-deaminated gliadin peptide IgA and tissue transglutaminase IgA. Therefore, the diagnosis of CD was made.

The patient was educated about the coexistence of SLE and CD in addition to SSc. She was also advised to be compliant on a gluten-free diet and treatment with hydroxychloroquine 200 mg daily, mycophenolate mofetil 500 mg twice daily, and prednisolone 30 mg, with a tapering dose. Due to her poor oral intake and her progressing dysphagia, along with her weight loss, she was kept on total parenteral nutrition to overcome malnutrition, and her weight increased by 2 kg over 10 days. She subsequently discharged home. Upon follow-up, 6 months later, the patient’s condition stabilized, with resolution of fever, pancytopenia, abdominal pain, and diarrhea. She had continued to gain weight. One year later, the patient had another follow-up, which showed resolution of her symptoms and improvement of her general health, as well as normalization of her body mass index. Her complete blood count was back to normal, except for normocytic normochromic anemia, which matched her baseline, and her complements normalized.

Discussion

The coexistence of SLE, SSc, and CD is extremely rare due to the distinct pathophysiological mechanisms of each disorder. While they involve different processes – autoantibody production in SLE, fibrosis in SSc, and a gluten-triggered immune response in CD – they share common features of autoimmunity and immune dysregulation. Given their rarity and the potential for overlapping symptoms, clinicians should be vigilant in considering the possibility of concurrent autoimmune diseases when diagnosing and treating patients.

Our patient had a unique presentation of CD and SLE that developed 9 years after the onset of SSc. To the best of our knowledge, there are no previous case reports documenting the coexistence of SSc, SLE, and CD.

Patients with a history of one autoimmune disease have roughly a 25% chance to acquire an additional type of autoimmune pathogenic disorder [10]. Many factors, including common pathogenic processes, genetic predisposition, and unknown reasons, contribute to the initiation of related disorders [11]. In our case, the patient was a known case of SSc who presented with suspicious clinical presentation for coexistence of another autoimmune pathology. Therefore, further investigation was required, and the patient later received a diagnosis of SLE and CD, based on their diagnostic criteria.

Forbess et al retrospectively examined the prevalence of CD in patients with SSc and found 4% of their patients with SSc had CD [7]. This was lower than what was previously reported by Rosato et al. This difference is mainly related to the methodology used to diagnose CD [7], whereas the latter depended mainly on CD serology [12].

The association between CD and SLE has been reported previously in some case reports. A study published in 2012 showed increased prevalence of SLE among patients with CD, with 3-fold increased risk, compared with that of the general population, however, with a low absolute risk [13]. The association between SLE and SSc is well established in the literature as a part of overlap syndrome [9,14]. A cohort study examining the prevalence of SSc-SLE overlap found a 6.8% occurrence, indicating that this overlap is relatively common among patients with SSc [9].

Regarding MAS, SSc is considered as a part of MAS type 2, and SLE is classified as a part of MAS type 3. Despite the fact that CD is an important autoimmune pathology, it is not considered in the classification of MAS types [10,15] (Table 1).

Conclusions

This case study represents, to the best of our knowledge, the first documented instance of the coexistence of SLE, SSc, and CD in a single patient, highlighting the extreme rarity of such a multifaceted autoimmune presentation. Although the coexistence of SLE, SSC, and CD is rare, as each has distinct pathophysiology, they share a common tendency toward autoimmune dysregulation. Clinicians should be vigilant in considering multiple autoimmune disorders when symptoms overlap.

What is interesting about the patient in our case is that she presented with 3 different types of autoimmune disorders, which fits the criteria and definition of MAS. However, this case cannot be classified into any subcategory of the already known MAS types, as the combination of SLE, SSc, and CD does not fit into any type of MAS.

It is important to consider investigating for other autoimmune syndromes, as clinically indicated, when facing a patient with one autoimmune disease, as it could be a part of overlap or MAS, and directing investigations based on clinical presentation, as even a rare association can be present.

Further research is essential to better understand the coexistence of autoimmune diseases, as their diagnosis can be challenging, due to complex and overlapping mechanisms. Investigating genetic, environmental, and immune factors could improve diagnostic accuracy and enhance patient care.