20. A challenging diagnosis of adult-onset Still’s disease in the setting of raised anti-streptolysin O titres

Abstract

Introduction We describe a case of a 40-year-old male with recurrent episodes of fever, polyarthralgia, myalgia and pharyngitis. Investigations revealed intermittent transaminitis and high serum ferritin, but also positive streptococcal serology, despite negative microbiology. This case illustrates the challenges faced when diagnosing adult-onset Still’s disease (AOSD) and distinguishing between alternative diagnoses, such as post streptococcal reactive arthritis (PSRA). It is important to differentiate between these conditions as they have different organ involvement, monitoring requirements, treatments and prognoses. This case has prompted a review of studies where the frequencies of clinical and serological features are noted in these two conditions. Case description A 40-year-old male was referred to acute medicine with 3 months of headache, fatigue, polyarthralgia, myalgia, night sweats, lymphadenopathy and otalgia. He reported a severe pharyngitis at symptom onset, 12 weeks earlier, for which he was given 20 days of phenoxymethylpenicillin by his GP. His sore throat improved, but his other symptoms persisted. His GP then suspected sinusitis, so prescribed doxycycline. He had no significant past medical history other than a tonsillectomy in his 20s and had been on no regular medication. On admission, he reported fever, headache, sweats, myalgia and arthralgia of the elbows and wrists. He had no meningism and denied any rashes, nasal discharge, joint swelling, neurological symptoms, weight loss or symptoms to suggest underlying malignancy. An ENT specialist felt sinusitis to be unlikely. On examination, the initial positive findings included tenderness of the right mastoid process, low grade cervical lymphadenopathy, tender wrists, erythematous pharynx and myalgia of the thighs. There was no rash, clinical synovitis, or organomegaly. Investigations included: Throat cultures: negative; Urine dip: trace blood; Anti-Streptolysin O Titres (ASOT): 1600 units/ml; Anti-DNAse B titres: 800; WCC: 16, neutrophils: 73%; ESR: 62; CRP: 120; Ferritin: 1322 (5x upper limit of normal); Transaminitis: ALT: 234, AST: 123; LDH: 428; CK: 47; ANCA, ANA, rheumatoid factor, anti-CCP, CMV, EBV, hepatitis A, B & C, HIV: negative; Echocardiogram: normal; CT head, chest, abdomen, pelvis: normal Our patient was referred to rheumatology and treatment for presumed AOSD was commenced with 30mg prednisolone (weaning dose) and methotrexate. His arthralgia and systemic symptoms vastly improved within one month. At that stage his ASOT was noted to have risen further to 3200 units/ml. He has stopped all medications after one year of treatment. Two months after cessation of methotrexate he remains asymptomatic, with marginally elevated ferritin but otherwise normal routine bloods. Discussion This case illustrates the difficulties involved in establishing an AOSD diagnosis. Despite meeting the Yamaguchi criteria, serositis, maculopapular rash and documented quotidian fever were absent. ASOT levels were elevated and rose after presentation, whilst pharyngitis had been evident at symptom onset, which could imply an alternative differential of PSRA. Identification of AOSD is important as it necessitates monitoring for cardiopulmonary manifestations and rarely macrophage activation syndrome. In AOSD, IL6-IL1 blockade is used for recalcitrant disease. For PSRA, it is important to ensure there are no features of acute rheumatic fever, renal disease, or cardiac disease. PSRA was less likely due to liver and ferritin abnormalities, which persisted long after CRP normalisation, persistent lymphadenopathy and negative throat swabs. The rise in ASOT was considered a false positive. The table compares clinical and serological features for the conditions. Table: Clinical and laboratory features in AOSD and PSRA AOSDPSRACLINICALJointsMild, oligoarticular and transientMay evolve into severe, destructive polyarticular formNon-migratory symmetrical polyarthritisUsually resolves in weeks but can last for monthsPredominantly affects knees, ankles and wristsRashEvanescent salmon pink macular/maculopapularOccurs with feverKoebner phenomenon (73%)Scarlatine rash at disease onsetGuttate psoriasisErythema nodosum/multiformeLeukocytoclastic vasculitisFeverDaily/twice daily lasting less than 4 hoursMay be present at initial point of infectionPharyngitisFrequently (70%)Usually precedes joint symptoms by 14 daysLiver50%No dataSpleen50%No dataCardiacPericarditis, myocarditis (30-40%)No increased risk in adultsPulmonaryPleuritis, transient pulmonary infiltrates (30-40%)No dataHaematologicalTTP/HUS/MAS (rare)No dataSEROLOGICALPositive Rheumatoid Factor0-7%0%Positive ASOTNo data82-100%ComplementNo dataNormal in 100%Deranged LFTs35-76%17%Hyperferritinaemia86-100%No dataRaised ESR100%76-100%Raised CRP100%100%Leucocytosis67-81%12-47%Anaemia62%No data Key learning points There can be diagnostic uncertainty regarding the diagnosis of AOSD, particularly as other conditions may share clinical features, such as recurrent pharyngitis with polyarthralgia/arthritis. PSRA is an important condition to keep in mind when investigating and managing these patients. Both conditions can present with polyarthralgia, but the chronic arthritis of AOSD can progress to destructive arthropathy. The rashes in both conditions generally differ, helping to distinguish between the two. Persistent pyrexia and pharyngitis would be rare in PSRA unless the patient is having recurrent streptococcal infections. Therefore, it is important to perform ENT examination with bacterial throat swabs and for the patient to keep a fever diary. Similarly, cervical lymphadenopathy should only be present during the acute phase of the streptococcal infection rather than persistently, as in the case of AOSD. Hepatosplenomegaly and haematological manifestations are more strongly associated with AOSD, so if these features are present there is greater diagnostic certainty, as long as infection and malignancy can be ruled out. ASOT can be falsely positive due to cross reactivity with myeloma, liver disease, hypergammaglobulinaemia, and autoimmune disease associated with increased rheumatoid factor. ASOT levels peak at 3 weeks and decrease at 8 weeks, and only decreases to pre-infectious levels at 8 months. Anti-DNAse B peaks at 6-8 weeks, decreases at 12 weeks and returns to pre-infectious levels at 12 months. Therefore, the timeline of possible streptococcal infection is important, as even if the infection was months prior, ASOT may be elevated. Repeating both titres is useful, as a disproportionate rise in anti-DNASe B compared with ASOT suggests an acute infection. ASOT may remain elevated for many months in the pharyngeal carrier state. It would be interesting to clarify the experience of other centres in the identification of raised ASOT in AOSD. Conflicts of interest The authors have declared no conflicts of interest.

Refractory Urticaria with Raised Antistreptolysin O (ASO) Titer: An Intriguing Case of Adult-Onset Still’s Disease

“…Unfortunately, that testing was not conducted in our case. In 1 notable case of AOSD, the patient had a clinical course similar to ours, with full clinical and laboratory remission but an elevated ASO titer [ 10 ]. Other reported cases suggest that the increase in the titer is a trigger for AOSD [ 11 ], while in 1 case, the titer fell after the disease was controlled [ 12 ].…”