Adult-onset Still’s disease revealed by a complete atrioventricular block, totally regressive under corticosteroid therapy

Abstract

We report the case of a 40-year-old veterinary surgeon who was admitted for spiking fevers, arthralgia, and a complete atrioventricular block. Tests revealed an inflammatory syndrome, hepatic cytolysis, neutrophilic leukocytosis, and increased troponin levels. Cardiac magnetic resonance imaging showed a small myocarditis but no tissue abnormality on the conduction pathways. In the absence of evidence-based infection and favorable evolution under broad spectrum antibiotherapy, an adult-onset Still’s disease was suspected and corticosteroid therapy administered. Evolution was then impressively favorable, with a persistent sinus heart rhythm 3 days later.

Learning objective: Febrile conductive disorders occurring during a systemic disorder with negative infection and auto-immunity work-up should lead to consider an adult-onset Still’s disease, which can be treated and cured, especially with steroids. Moreover, fever, polyarthritis, neutrophilic leukocytosis, pericarditis, and myocarditis should lead to consideration of adult-onset Still’s disease.

Introduction

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder whose pathogenesis is largely unknown. Some patients develop organ failures that can be life-threatening such as respiratory or cardiac manifestations. Instances of myocarditis have been described within the range of cardiac complications. Here we present a case of AOSD, detected thanks to, among other things, a complete atrioventricular (AV) block, which spectacularly regressed under corticosteroid therapy.

Case report

AOSD is a rare systemic immune-mediated inflammatory disorder (IMID) classically exposed by the triad of fever, salmon rash, and arthralgia. Blood tests frequently demonstrate marked inflammation, neutrophil polynucleosis, hepatitis, and hyperferritinemia [1]. Some patients develop organ failures that can be life-threatening such as respiratory failure, shock, coagulopathy, or cardiac manifestations [2]. Among the latter, pericarditis is common, and can lead to cardiac tamponade. Instances of myocarditis have been described within the range of cardiac complications but unlike other immune-mediated diseases such as sarcoidosis, heart-block has been rarely reported. Here we present a case of AOSD, detected thanks to, among other things, a complete AV block, which regressed under corticosteroid therapy.

This 40-year-old veterinary surgeon had a medical history of right clubfoot, traumatic wound of right Achilles’ tendon requiring flap in 2017, quit smoking <10 pack-years, and no recent trip abroad.

He had been suffering for a week from spiking fevers (reaching up to 39 °C), asthenia, and diffuse myalgia. Prior to admission, he had been self-medicating with paracetamol and ibuprofen for 5 days.

Confronted with the manifestation of chest pain punctuated by breathing, bradycardia at 40/min, and arthralgia, he consulted his general practitioner who referred him to his local emergency department. The patient was then transferred to the cardiology department.

Clinically, his weight was 88 kg for a height of 180 cm. The pulse reached 40/min, the blood pressure was 112 mmHg/82 mmHg. A fluctuating high-grade fever spiked predominantly in the evening. He had chest pain comparable to pericarditis, but no dyspnea. Cardiopulmonary auscultation was normal. There was no acute abdomen, the latter was pain-free. There was no rash, ganglionic areas were clear. He had arthritis in the metacarpophalangeal joint of the 2nd and 3rd fingers in his right hand, in his left wrist, and left ankle. The ear–nose–throat examination gave normal results.

The electrocardiogram carried out on arrival revealed a complete AV block (Fig. 1) with a junctional escape at 60/min alternating with a ventricular escape at 40/min.

Fig. 1.

Electrocardiography carried out on arrival revealed a complete atrioventricular block with a ventricular escape at 40/min, alternating with a junctional escape at 60/min at other times.

A transthoracic echocardiography was performed and showed no morphological abnormality, the left ventricular ejection fraction was normal, neither kinetic disorder nor valvulopathy were found. It exposed a pericardial effusion near to the inferior and inferolateral walls reaching 10 mm, with no consequence.

The biological analyses demonstrated acute kidney failure (serum creatinine 265 μmol/L against 87 μmol/L five days previously) with proteinuria at 5.09 g/g (<0.5), increased troponins at 150 ng/L (<14), inflammatory syndrome with C-reactive protein increased to 300 mg/L (<5), increased serum ferritin to 2389 μg/L (30–400), hepatic cytolysis: aspartate aminotransferase (AST) 78.9 IU/L (0–51) and alanine aminotransferase (ALT) 289.5 IU/L (0–51), as well as a neutrophilic leukocytosis which remained stable at 17 000/mm³ (1700–7500). There was no hemolysis.

Differential diagnosis evoked

• •Infection:

Leptospirosis

Lyme disease

Q fever

Endocarditis

Pyogenic septicemia

Viral hepatitis, human immunodeficiency virus (HIV)

• •IMID:

AOSD

Systemic lupus erythematosus

Sarcoidosis

Investigations

- Initial acute kidney failure motivated further analyses:

• •Kidney ultrasonography: no abnormalities in particular obstructive.
• •Kidney biopsy: No significant glomerular lesion, focal acute tubulopathy. Isolated mesangial C3 deposits on immunofluorescence.
• •Follow-up: spontaneous full recovery. Renal failure was considered multifactorial (non-steroidal anti-inflammatory drugs, bradycardia).

- Cardiac explorations performed to determine cardiac involvement:

• •Cardiac magnetic resonance imaging (MRI): showed subepicardial enhancement of the anterolateral wall at the distal mid-third junction (Fig. 2) associated with pleural effusion, pericardial effusion. No kinetic disturbance — thus evoking a myopericarditis. No tissue abnormality on the conduction pathways.
• •Coronary angiography: normal.

Fig. 2.

Cardiac magnetic resonance imaging, T1 late gadolinium enhancement sequence, showed subepicardial enhancement of the anterolateral wall.

- Suspecting a systemic infection or sepsis-like IMID, the following examinations were performed:

• •Thoracic-abdominal-pelvic tomodensitometry: no abnormality found.
• •Positron emission tomography/computed tomography (PET/CT): Hyperfixation of the mitral valve papillary muscles and basal lateral wall - unspecific. Single right axillary lymph node hypermetabolism. Strengthening of osteomedullary and splenic homogeneous fixation related to the inflammatory syndrome.

- Auto-immune analysis (antinuclear antibodies, rheumatoid factors, anti-neutrophil cytoplasmic antibodies, anti-cyclical citrullinated peptide antibodies, anti-myeloperoxidase antibodies, anti-glomerular basement membrane antibodies, anti-proteinase 3 antibodies) negative.

- Infectious blood tests:

• •Repeated negative hemocultures.
• •Serology Q fever, Lyme, brucellosis, leptospirosis, polymerase chain reaction (PCR) leptospirosis: negative. PCR cytomegalovirus, adenovirus, human herpesvirus 6, parvovirus B19: negative.
• •Viral hepatitis serologies, HIV: negative.

- Sarcoidosis was also considered:

• •No mediastinal lymph node nor lung infiltrate on CT.
• •Angiotensin-converting enzyme: normal 41 IU/L (5–60).

Management

Given this clinical presentation: Febrile arthromyalgia with myopericarditis, an infectious pathology such as leptospirosis was first suspected, especially due to the patient's occupation (veterinary surgeon); a broad-spectrum antibiotic therapy with 3rd generation cephalosporine (ceftriaxone) and doxycycline was introduced.

In the absence of a favorable evolution after 7 days of broad spectrum antibiotherapy, and confronted with a persistent spiking fever, worsening polyarthritis and a neutrophilic leukocytosis with an absence of evidence-based infection, interdisciplinary discussion raised the hypothesis of AOSD. Myocarditis is an infrequent but classical complication of the disease; moreover, rare cases of conductive disorders were already reported in the literature [3], [4]. The diagnosis of AOSD relies on the clinico-biological presentation of the patient and exclusion of differential. A decision was made to introduce a high-dose corticosteroid therapy (methylprednisolone): 8 mg/kg/day for 3 days then 1 mg/kg/day. Of note, our patient fulfilled both Yamaguchi and Fautrel criteria. He had Yamaguchi major criteria: fever + arthralgia + neutrophil leukocytosis; and minor criteria: negative antinuclear antibody and negative rheumatoid factor + liver dysfunction (high AST/ALT) + lymph node enlargement (right axillary lymph node hypermetabolism on PET/CT).

Despite a major alteration of the patient's condition since his admission, the evolution was spectacularly favorable under corticosteroids: conductive disorders regressed within the first twenty-four hours, the rhythm was persistent sinusal (Fig. 3) after three days of corticosteroid therapy.

Fig. 3.

Electrocardiogram after 3 days of corticosteroid therapy showed sinus rhythm. Continuous monitoring showed persistent sinus rhythm.

The patient became apyretic, joint pain resolved, and inflammatory syndrome decreased (Fig. 4).

Fig. 4.

C-reactive protein (CRP), creatinine, heart rate, and troponin T, function of time.

With regard to acute kidney failure, which spontaneously improved and normalized before corticosteroid therapy, a renal biopsy was inconclusive, but spontaneous recovery (before initiation of steroids) led to suggest an iatrogenic etiology (self-medication with non-steroidal anti-inflammatory drugs in the context of moderate low-cardiac flow relative to bradycardia).

The patient was discharged from hospital at day 16 of hospitalization, 7 days after steroids initiation.

Follow-up

Close follow-up was provided both in the departments of cardiology and internal medicine. Corticosteroid therapy was progressively decreased and ended after 8 months of treatment. A control cardiac MRI was performed after 6 months and showed fibrous sequela of minor myocarditis. A rhythmic Holter examination did not show any conductive disorder but exposed many ventricular extrasystoles with no sustained phenomenon. The patient remains asymptomatic, without fever or inflammatory syndrome, he has returned to work. Fourteen months after hospital discharge, he is in complete drug-free remission, with normal electrocardiogram.

Discussion

Cardiac damage due to AOSD can be serious, with pericarditis (including tamponade), myocarditis (sometimes associated with arrhythmia [5]). Conductive disorders are rarely reported (only two cases found in the medical literature [3], [4]). In the case presented here, the patient's occupation (veterinary surgeon) misled us to suspect an infectious disease such as leptospirosis or Lyme disease, we carried out both analyses twice before shifting our focus to an IMID. The results of auto-immune screening were negative. Interdisciplinary discussion led to recognize some simple clues that are suggestive of AOSD (high-grade fever, polyarthritis, neutrophilic leukocytosis, pericarditis). Our patient met both Yamaguchi and Fautrel criteria. Complete response to steroids further confirmed the diagnosis. This case suggests that conductive disorder occurring during a systemic disorder should lead physicians to suspect an AOSD.

Conclusion

This 40-year-old veterinary surgeon had an AOSD revealed by spiking fevers, polyarthritis, neutrophilic leukocytosis, myopericarditis, and a complete AV block. Regression of symptoms including conductive disorders was spectacular under corticosteroid therapy.

Conflict of interest

The authors declare that there is no conflict of interest.