A Clinician’s

Pearls & Myths

In Rheumatology
John H. Stone, M.D., M.P.H.
Professor of Medicine
Harvard Medical School
The Edward A. Fox Chair in Medicine
Massachusetts General Hospital
Disclosures ACKNOWLEDGEMENT
Autoimmunity Center of Excellence grant
• Abbvie - consulting NIH/NIAID: UM1 AI-144295
• Amgen – consulting
• Bristol-Myers Squib – grants, consulting
• Chemocentryx – consulting
• Horizon - grants, consulting
• Novartis - consulting
• Roche/Genentech – grants, consulting
• Sanofi - grants, consulting
• Spruce Biosciences – consulting
• Steritas - consulting
 MYTH:
Symmetrical polyarthritis at presentation
is the rule.
REALITY: Symmetry may not be present in early RA.
Two other common presentations:

• Asymmetric oligoarthritis

• Migratory oligoarthritis

Serologies are important in both of these settings.

PEARL: A migratory oligoarticular arthritis also
brings to mind…?
• Favors lower
extremitities.

• Quickly forgotten once

treatment begins.

• Often heralds a flare.

ANCA-associated vasculitis: GPA or MPA

 MYTH:
RA improves dramatically in pregnancy.

Reality:
Only partly true. DAS28 remission occurs in only 25%.

Flares occur in 29%.

Discontinuation of effective therapy may partly explain this.

Post-partum flares occur in 47% of RA pregnancies.

Jethwa, 2019; van den Brandt, 2017

PEARL:
The first step in identifying abnormality in a lupus pregnancy
is understanding the physiology of a normal pregnancy.
 MYTH:
Serum complement levels are the Rosetta Stone for
understanding lupus activity in pregnancy.
It is true that hypocomplementemia…

- Predicts preterm birth if before pregnancy.

- Predicts pregnancy loss if observed in first trimester.
REALITY: Complement levels INCREASE 10-50% in normal pregnancies.

• Trends more helpful than any single measurement.

• Complement levels alone seldom provide definitive direction.

Hiramatsu, 2021; Mankee, 2015

PEARL: Rising proteinuria in a pregnant lupus patient may be OK.

COMMENT: Maternal blood volume increases by 50% in pregnancy

(and so does the GFR).

Proteinuria can double in pregnancy

simply because of increased renal perfusion.
 PEARL:
A creatinine value of 1.0 mg/dL
is likely to be abnormal.

COMMENT: Maternal blood volume increases by 50% in pregnancy.

• Physiologic lowering of the serum creatinine level.

• Normal creatinine is between 0.4-0.7 mg/dl.
• 1.0 mg/dL may be a cause for concern.
PEARL: Raynaud’s is usually the first sign of SSc.
There is one important exception...

COMMENT:
Patients with
anti-RNA polymerase III abs.

Implication:
Scleroderma renal crisis may
bring systemic sclerosis to
medical attention.
 Successful ACEi

Permanent
dialysis

Died early
 MYTH:
ACE inhibitor should be used as prophylaxis.

REALITY:
ACEi prophylaxis may set up a chronic, less reversible process.

Best outcomes occur in patients with high BP but low creatinine.

“The pulmonary and submandibular
gland findings are virtually identical:
necrosis, giant cells, and arteritis.
The diagnosis of GPA is favored.”
PEARL: GPA patients can have submandibular gland enlargement.
And lacrimal gland enlargement (dacryoadenitis).

COMMENT: The differential diagnosis of dacryoadenitis is short:

• Sj⍤gren’s syndrome
• Sarcoidosis
• IgG4-related disease
• AL amyloidosis
PEARL: GPA patients can have submandibular gland enlargement.
And lacrimal gland enlargement (dacryoadenitis).

COMMENT: The differential diagnosis of dacryoadenitis is short:

• SjÖgren’s syndrome
• Sarcoidosis
• IgG4-related disease
• AL amyloidosis
• Granulomatosis with
polyangiitis
 GPA & IgG4-RD: Clinical Doppelgangers

GPA
Meninges Hypertrophic pachymeningitis
Pituitary Hypophysitis
Orbits Pseudotumor, extra-ocular muscles
 GPA & IgG4-RD: Clinical Doppelgangers

GPA
Meninges Hypertrophic pachymeningitis
Pituitary Hypophysitis
Orbits Pseudotumor, extra-ocular muscles
Upper airway Subglottic stenosis

Lungs Nodules & multiple other findings

Kidneys Renal masses (GN)
 GPA & IgG4-RD: Clinical Doppelgangers

GPA IgG4-RD
Meninges Hypertrophic pachymeningitis Hypertrophic pachymeningitis
Pituitary Hypophysitis Hypophysitis
Orbits Pseudotumor, extra-ocular muscles Pseudotumor, extra-ocular muscles
Upper airway Subglottic stenosis Supraglottic inflammation
more likely
Lungs Nodules & multiple other findings Nodules & multiple other findings
Kidneys Renal masses (GN) Renal masses (GN)
Staining for
IgG4 does
NOT
differentiate
these two
diseases.

IgG4-RD GPA
Neither does
storiform
fibrosis.

IgG4-RD GPA
PEARL: You can hang your hat on three findings…

These do NOT occur in IgG4-RD.

1. Granulomatous inflammation
2. Necrosis
3. Neutrophilic inflammation
 PEARL:
Serology is the other key to distinguishing IgG4-RD from AAV.

• NOT serum IgG4

elevation

•ANCA
 PEARL:
Once the diagnosis of IgG4-RD is established, serum IgG4
concentrations are a reliable reflection of disease activity.

COMMENT:
• Serum IgG4 is a good biomarker in IgG4-RD.

• If elevated at baseline, it correlates well with disease activity.

• The higher the baseline value the better the correlation.

• Declines with treatment, rises with returning activity.

 MYTH:
Lyme arthritis only presents in the summer.

COMMENT:
Acute Lyme disease
typically occurs in summer
months.

Lyme arthritis can present

at any time of the year.

Schwartz, 2017
 PEARL:
Another thing to think about in a teenager with a
monoarthritis of the knee…
Juvenile spondyloarthropathy:
• Presents with asymmetric oligoarthritis: lower extremity
involvement predominates.
• Starts with peripheral arthritis and/or enthesitis or uveitis.
• “Enthesitis-related arthritis” (ERA): high risk of ultimately
developing ankylosing spondylitis.
PEARL: Three useful ophthalmologic acronyms…

“KP” – Keratic precipitates

“PUK” – Peripheral ulcerative keratitis
“IOI” – Idiopathic orbital inflammation
 “Mutton fat” KP

“Granulomatous uveitis” usually

denotes sarcoidosis.

Non-granulomatous diseases can

also cause “granulomatous uveitis”.

Katz G et al., 2021

PEARL: PUK is a rheumatologic emergency.
COMMENT: PUK often associated with a lethal disease.

Two diagnoses:

• Rheumatoid arthritis

• ANCA-associated vasculitis
“Idiopathic” Orbital Inflammation (IOI)
 PEARL:
One cannot make a diagnosis of IOI or
“idiopathic” ANYTHING if the work-up is incomplete.

FINAL PATHOLOGIC DIAGNOSIS:

A. RIGHT INFERIOR RECTUS MUSCLE:
DIAGNOSIS: GRANULOMATOUS MYOSITIS.

Scattered, compact, non-necrotizing granulomas with

occasional giant cells are appreciated within the muscle
fibers, disrupting the normal muscle architecture.
PEARL:
A 120 year-old (!)
African-American man with
intense inflammatory
polyarthritis and mental status
changes.
• ”Shocking” change in appearance and mental status
• Barely recognized his nephew

• Had previously ambulated well with cane

• Could now not stand

• “Considerable discomfort from joint pains in wrists,

hands, elbows, shoulders, and back”
• Groaning in pain
• Needed a neck brace to keep his head up
Examination:

A diagnostic test was performed:

Bone Joint Surg Am 1964;46:1753-4.
ACUTE CERVICAL PAIN ASSOCIATED WITH RETROPHARYNGEAL CALCIUM DEPOSIT. A CASE REPORT
J HARTLEY

Crowned Dens Syndrome

Crowned Dens Syndrome
• Dramatic presentation

• Can mimic GCA/PMR, meningitis, sepsis

• Often occurs with peripheral joint involvement

• CT or MRI key to diagnosis

• Exquisitely responsive to prednisone

THANK YOU!
Lyme disease
Schwartz, 2017, Selected References:
MMWR Surveill Summ
SLE & pregnancy
IgG4-RD Jethwa, 2019, J Rheumatol
Katz, 2021, Rheumatol Van de Brandt, 2017, Arthr Res Ther
Hiramatsu 2021, Arthr Res Ther
Mankee, 2015, Lupus Med Sci

Scleroderma
Steen, 1990, Ann Intern Med
Steen, 2000, Ann Intern Med