Fatal lupus flare presented as syndrome of inappropriate antidiuretic hormone secretion and hemorrhagic gastroenteritis: a case report

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BACKGROUND

Systemic lupus erythematous (SLE) is a chronic autoimmune disease with possible multiple organ involvement. The incidence rate is 6.73 cases per 100,000 individuals per annum and prevalence of 134 per 100,000 individuals in the U.S. Caucasian and European populations. The course of the disease may vary greatly with a broad range of presentations from mild to severe and even life-threatening symptoms. It may have unusual manifestations, making the diagnosis challenging and delaying treatment [1–3]. Although not rare, SLE can be challenging to recognize because of multiple clinical symptoms and their combinations [4, 5]. Patients with a severe SLE flare are especially prone to infections, including pulmonary infections—a major cause of hospitalization and mortality in patients with SLE [6]. It is worth emphasizing that timely diagnosis may be crucial for patient survival.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with SLE has been rarely reported; today, it is recognized more often [7, 8]. Though it is sometimes attributed to other causes, such as medications, this condition is considered as a presentation of neuropsychiatric lupus. One of the possible pathogenetic mechanisms of hyponatremia in SLE is SIADH caused by hypophysitis [9–11] or inflammation-driven non-osmotic vasopressin release [12]. Thus, SIADH as a presentation of neuropsychiatric lupus correlates with the disease activity [13, 14] and development of psychosis [15]. To diagnose SIADH, it is usually required to assess the volume status, measure urine and plasma sodium, and rule out other causes of hyponatremia [16].

Lupus enteritis is also a rare but potentially lethal manifestation of SLE as it may evolve to intestinal necrosis and perforation if untreated [17–19]. Abdominal computed tomography (CT) imaging is the method of choice that should be requested when lupus enteritis is suspected. Common CT findings include the target sign (bowel wall thickening > 3.0 mm), the comb sign (engorgement of mesenteric vessels), and the increased attenuation of mesenteric fat. Glucocorticoids are often the first-line treatment of lupus enteritis [20].

We describe the case of a 34-year-old man who had no history of SLE. He presented with severe hyponatremia and signs of enteritis and developed hemorrhagic gastritis soon afterwards.

DESCRIPTION OF THE CASE

Anamnesis

A 34-old man was brought to our emergency department by his wife in October 2019 because he had become disoriented. According to the patient’s wife, he had up to four loose stools a day for 3–4 days before admission.

He had been diagnosed with epilepsy 6 months before when he started to have generalized seizures. However, he had not had such episodes for the previous five months and had not taken any anticonvulsants. He was in his usual health until two months earlier when he developed a daily fever up to 38.5 °C, fatigue, and myalgia in the upper back and shoulder and hip girdles. A month before admission he developed diarrhea and fever up to 39 °C and was prescribed with antibiotics by a primary care physician. Soon he developed a widespread rash all over the body, which was considered an allergic reaction. At the time, he was admitted to the infectious disease department, where they thoroughly searched for infections that might cause his symptoms. Multiple stool and blood tests came back negative, including for Salmonella spp., Shigella spp., Yersinia spp., and Clostridioides difficile. The patient was treated with glucocorticoids and antibiotics for a week in other hospital. All his symptoms resolved completely after treatment, and he did not seek any medical attention until the day of admission to our hospital.

Diagnostic Assessment

On physical examination, the patient was agitated and disoriented with incoherent speech. His lungs were clear on auscultation, heart rate was regular, and no murmurs were heard. Vital signs: blood pressure of 140/80 mmHg, heart rate of 112 bpm, respiration rate of 20 breaths per minute, oxygen saturation of 98% while breathing on ambient air, and temperature of 37.3 °C. The abdomen was non-tender and non-distended with active bowel sounds. No hepatosplenomegaly or peripheral lymphadenopathy were detected. Rectal examination showed brown stool without blood or mucus. Oral examination revealed grayish-white sores on patient’s palate and buccal mucosa.

The laboratory findings were remarkable for sodium of 103 mmol/L, potassium of 2.5 mmol/L, ALT of 97 IU/L, AST of 261 IU/L, alfa-amylase of 117 IU/L, creatine kinase of 682 IU/L, albumin of 19 g/L, CRP of 10 mg/L. Blood urea nitrogen, creatinine, glomerular filtration rate, and bilirubin were normal. A complete blood count with differential revealed mild normocytic anemia with Hb of 11.6 g/dL, moderate thrombocytopenia with platelet count of 69,000/µL, and severe lymphopenia with lymphocyte count of 180/µL. Urine sodium was as high as 160 mEq/L, allowing to diagnose SIADH. Head CT was unremarkable. Chest СT (see Fig. 1) revealed normal lungs without infiltrates and nodules. Abdominal CT showed jejunal loops with thickened enhancing walls (see Fig. 2, 3), suggestive of enteritis.

 

Fig. 1. Chest computed tomography image. Normal lungs; heart chambers with normal diameters.

 

Fig. 2. Abdominal computed tomography image, axial slices: a, computed tomography image after intravenous enhancement, arterial phase; b, computed tomography image without intravenous contrast enhancement. Arrows show jejunal loops with thickened walls.

 

Fig. 3. Abdominal computed tomography image, frontal reformation after intravenous enhancement, arterial phase. Arrows show jejunal loops with thickened walls.

 

The patient’s hyponatremia was managed slowly over a few days; at day 3 the patient was completely alert and oriented. He continued to have 3–4 loose stools a day but otherwise remained stable until day 4 when he was found to have melena, cough, and dyspnea. On physical examination, new skin changes resembling Janeway lesions were found on palms and soles along with bilateral hypothenar erythema (see Fig. 4). Vital signs were as follows: BP of 120/80 mmHg, heart rate of 130 bpm, respiration rate of 24 breaths per minute, oxygen saturation of 92% on ambient air, and a temperature of 37.6 °C.

 

Fig. 4. Janeway lesions on the patient’s palms and soles.

 

Blood tests showed a profound drop in hemoglobin and platelet count and increase in band form count from 18 to 62%. The CRP increased up to 134 mg/L.

Upper gastrointestinal endoscopy revealed diffuse bleeding from gastric mucosa. Chest CT showed bilateral lower-lobe infiltrates and partial atelectasis, suggestive of pneumonia (see Fig. 5). Bronchoalveolar lavage fluid was submitted for culture.

 

Fig. 5. Second chest computed tomography image. Bilateral infiltrates and partial atelectasis in the both lower lobes: a, axial slice; b, frontal reformation.

 

Transthoracic echocardiography followed by transesophageal echocardiography both revealed vegetation on right coronary and non-coronary aortic valve cusps (see Fig. 6, 7).

 

Fig. 6. Results of transesophageal echocardiography. Mid-esophageal aortic valve, long axis. Vegetation on non-coronary and right coronary cusps (arrows) in systole (a) and diastole (b).

 

Fig. 7. Results of transesophageal echocardiography. Mid-esophageal aortic valve, short axis. Vegetations on non-coronary and right coronary cusps (arrow).

 

Three blood samples were submitted for culture and empiric therapy with intravenous antibiotics was initiated.

At day 5, HEp-2-IFA showed the presence of antinuclear antibodies with the titer of 1:5120, a homogeneous fluorescence pattern, a low level of C3 and C4 complement components, and anti-dsDNA antibody positivity. Thus, treatment with intravenous methylprednisone 2 mg/kg/day was initiated at day 5.

Follow-Up and Outcomes

There was some improvement in patient’s dyspnea with increased oxygen saturation and lower heart and respiratory rates. However, the patient still had intermittent gastric bleeding, requiring daily transfusions of packed red blood cells, fresh frozen plasma, and platelets. At day 7, the patient developed rapid respiratory failure requiring invasive mechanical ventilation. Antibacterial treatment was adjusted for the bronchoalveolar lavage fluid culture findings and the dosage of methylprednisolone was increased to 1000 mg/day. Despite treatment, the patient’s respiratory function continued to deteriorate. He developed severe hypoxia, hypercapnia, and respiratory acidosis and died at 30 hours of mechanical ventilation.

Histopathological Findings

The autopsy revealed aseptic verrucous endocarditis of the aortic valve (see Fig. 8), local myocardial scarring without any evidence of coronary artery disease, and non-occlusive thrombosis of the common ileac artery, severe intestinal wall edema with mucosa atrophy, and pneumonia with subtotal involvement of both lungs and signs of destruction. Periarteriolar fibrosis (onion skinning) in the spleen was the only found sign of vasculitis (see Fig. 9).

 

Fig. 8. Autopsy material. Microscopic image of an aortic valve cusp. Nonbacterial endocarditis.

 

Fig. 9. Autopsy material. Periarteriolar fibrosis (onion skinning) in the spleen.

 

DISCUSSION

SLE is a chronic autoimmune disease of unknown cause that may affect any organ in the human body. Although it can have a relatively benign progression, in some patients it progresses rapidly with fulminant involvement of multiple organs [10–14]. For such patients, diagnosis delayed even for a few days can have catastrophic effects. However, symptoms of the disease may vary greatly, requiring a high level of clinical suspicion from physicians.

The patient did not have the verified diagnosis on admission and presentation of the disease was not quite typical. However, we can retrospectively assume that our patient had been suffering from SLE for at least six months before presentation. We hypothesize that seizures could be the first sign of the disease, reflecting repeated microembolic cerebral events. First, the patient developed the secondary antiphospholipid syndrome and Libman–Sacks endocarditis and had a potential source of emboli. Second, there were autopsy evidence of a previous embolic event, such as iliac artery thrombosis and myocardial scarring.

Recurrent gastric hemorrhage without obvious eliminable source was a big challenge in this case as the bleeding recurred despite adequate gastroprotection, even after the methylprednisone therapy had been initiated.

It is difficult to tell whether or not an acute lupus pneumonitis preceded the bacterial pneumonia, even with the available autopsy findings. However, we consider this scenario as quite possible given the extreme disease activity and multiple organ involvement in our patient. On the other hand, in this case, severe lymphopenia was a significant risk factor for major nosocomial infection.

CONCLUSION

To the best of our knowledge, this is the first reported case of lupus flare presented as combination of SIADH and hemorrhagic gastroenteritis. Both SIADH and enteritis are rare but potentially dangerous manifestations of lupus. Physician’s awareness of this possibility will prompt the diagnosis and may be crucial for early, potentially life-saving treatment. Diagnostic imaging (CT and echocardiography) in combination with clinical presentations of the disease and laboratory tests help to make a correct diagnosis.

ДОПОЛНИТЕЛЬНАЯ ИНФОРМАЦИЯ

Вклад авторов. К.С. Далгатова — курация и лечение пациента, написание черновика рукописи, редактирование текста рукописи; Д.П. Котова, М.А. Магомедов — курация и лечение пациента; А.Б. Хлавно, Е.С. Першина — курация пациента; А.А. Богданова — курация и обследование пациента; В.Е. Синицын — курация и обследование пациента, написание черновика рукописи, редактирование текста рукописи. Все авторы одобрили рукопись (версию для публикации), а также согласились нести ответственность за все аспекты настоящей работы, гарантируют надлежащее рассмотрение и решение вопросов, связанных с точностью и добросовестностью любой её части.

Этическая экспертиза. Неприменимо.

Согласие на публикацию. Авторы получили письменное информированное добровольное согласие супруги пациента на публикацию персональных данных, в том числе фотографий (с закрытием лица), в научном журнале, включая его электронную версию.

Раскрытие интересов. Авторы заявляют об отсутствии отношений, деятельности и интересов за последние три года, связанных с третьими лицами (коммерческими и некоммерческими организациями), интересы которых могут быть затронуты содержанием статьи.

Оригинальность. При проведении исследования и создании настоящей статьи авторы не использовали ранее полученные и опубликованные сведения (данные, текст, иллюстрации).

Доступ к данным. Редакционная политика в отношении совместного использования данных к настоящей работе не применима.

Генеративный искусственный интеллект. При создании настоящей статьи технологии генеративного искусственного интеллекта не использовали.

Рассмотрение и рецензирование. Настоящая работа подана в журнал в инициативном порядке и рассмотрена по обычной процедуре. В рецензировании участвовали три внешних рецензента.

ADDITIONAL INFORMATION

Author contributions: K.S. Dalgatova: supervision and treatment of the patient, writing the initial draft of the manuscript, editing the manuscript; D.P. Kotova, M.A. Magomedov: supervision and treatment of the patient; A.B. Khlavno, E.S. Pershina: supervision of the patient; A.A. Bogdanova: patient’s supervision and examination; V.E. Sinitsyn: patient’s supervision and examination, writing the initial draft of the manuscript, editing the manuscript. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: Not applicable.

Consent for publication: Written informed consent was obtained from the patient’s spouse for publication of the patient’s medical data, including photographs, in a scientific journal and its online version.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text, images, or data) was used in this study or article.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer-review process involved three external reviewers.

About the authors

Kira S. Dalgatova

Olymp Clinic Mars

Author for correspondence.
Email: kira_1975@mail.ru
ORCID iD: 0009-0007-3327-009X

MD

Russian Federation, Moscow

Daria P. Kotova

City Clinical Hospital No. 1 named after N.I. Pirogov

Email: doc.kotova@mail.ru
ORCID iD: 0000-0003-1071-0877
SPIN-code: 5690-4452

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow

Anna B. Khlavno

City Clinical Hospital No. 1 named after N.I. Pirogov

Email: Anna.khlavno@yandex.ru
ORCID iD: 0009-0004-5812-4070

MD

Russian Federation, Moscow

Alexandra A. Bogdanova

Olymp Clinic Mars

Email: doc.aabogdanova@gmail.com
ORCID iD: 0000-0002-0426-2636
SPIN-code: 3991-9420

MD

Moscow

Ekaterina S. Pershina

City Clinical Hospital No. 1 named after N.I. Pirogov

Email: pershina86@mail.ru
ORCID iD: 0000-0002-3952-6865
SPIN-code: 7311-9276

MD, Cand. Sci (Medicine)

Russian Federation, Moscow

Marat A. Magomedov

City Clinical Hospital No. 1 named after N.I. Pirogov

Email: mma16@bk.ru
ORCID iD: 0000-0002-1972-7336
SPIN-code: 6195-3616

MD

Russian Federation, Moscow

Valentin E. Sinitsin

Lomonosov Moscow State University

Email: vsini@mail.ru
ORCID iD: 0000-0002-5649-2193
SPIN-code: 8449-6590

MD, Dr. Sci. (Medicine) Professor

Russian Federation, Moscow

References

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