This document discusses various types of crystals found in rheumatology, including mono-sodium urate (gout), calcium pyrophosphate dehydrate (CPPD), basic calcium phosphate (BCP), cholesterol crystal, lipid crystal, and corticosteroid crystal. It presents several case studies demonstrating the clinical presentation and investigations for patients with these various crystal-related arthritides. Key points include the importance of identifying crystals in synovial fluid to confirm diagnoses, characteristic radiographic and ultrasound findings, and treatment approaches for acute flares and long-term management.

1. Crystals in rheumatic
diseases
Dr Ritasman Baisya
Assistant Professor , Rheumatology

2. Types of crystal in Rheumatology
• Mono-sodium urate – Gout
• Calcium pyrophosphate dehydrate ( CPPD)
• Basic calcium phosphate – BCP
• Cholesterol crystal
• Lipid crystal
• Cortcosteroid crystal

3. Case 1
• 53 M
• Episodic pain and swelling in dorsum of foot ,
predominantly Ist MTP for 4 years
• Admitted with both knee, MTP , ankle
synovitis with FC 4
• On and off NSAIDs
• Cr- 2.67 , RF- negative

4. Contd
• Synovial fluid from left knee – needle shaped crystal
• HRUS both knee , Ist MTP , left ankle – joint effusion , double contour
sign
• Diagnosed as Acute Gouty arthritis with NSAID induced AKI
• Treated with 30 mg wysolone for 5 days and pain relieved and AKI
gradually improved
• Started Colchicine ( prophylactic dose ) and ULT ( Febuxostat ) –
patient better

5. Case 2
• This is a case of middle-aged man with six months
history of inflammatory polyarthritis with tophaceous
swelling over hand.
• His uric acid level was high.
• Xray of hand showed soft tissue swelling of tophus
with large erosions in PIP.
• It is a case of Polyarticular tophaceous gouty arthritis.

6. Case 3
• 30-year-old male, occasional alcoholic , mild obese ( BMI- 29 )
• presented with episodic pain in right MTP joint , right knee joint
since two years , each episode lasted for 5-7 days , wholly relieved
with NSAIDs . His knee and foot X-ray was normal .
• High resolution ultrasound (HRUS) knee showed intratendinous
tophi in the patellar tendon ( Figure 1a) and peritendinous tophus
in the quadriceps tendon ( figure 1 b ) . No evidence of double
contour sign , His serum uric acid was 9.
• This was gouty arthritis with an unusual site tophaceous deposition

7. case 4
• This 60 year old male presented with multiple small and
large joint arthritis with olecranon bursitis .
• X-RAY BOTH FOOT showed joint space narrowing of
right 1st IP joint with osteophytes with subchondral cyst and
overhanging edges .
• Synovial fluid from right knee showed uric acid crystals
however uric acid was 6.3.
• Intracellular needle crystals ( crystals crossing neutrophils )
are more pathognomonic of Gouty arthritis ( Figure2 )

8. Gout and Urate crystallopathy
• Mainly episodic , LL predominant , started with Ist MTP often (
podagra )
• Worst pain in life , relieved with NSAIDS dramatically
• often present as red hot joint , septic arthritis is a differential
• Polyarticular presentation can be seen
• Almost absent in young female as estrogen has protective effect
• Post menopausal women and men are commonly affected
• Alcoholism and dietary life style strong risk factor

9. Investigation
• Needle shaped MSU crystal in synovial fluid is typical – intracellular
crystal pathognomonic
• Xray in chronic gout – large rat-bite erosion with over-hanging edge ,
preserved joint space till OA developed , soft tissue swelling due to
tophi
• US – tophaceous deposition, aggregates of crystals ,erosion , synovitis
, double contour sign
• DECT – this is newer technique, accurate assessment of the
distribution of the deposited monosodium urate (MSU) crystals in
gout and quantifies them.

10. MSU crystals
• strongly negatively birefringent needle-shaped objects, many of
which are intracellular, having been phagocytized by synovial fluid
leukocytes.

11. How to detect crystals
• Polarized microscopy
• slide , coverslip are free of dust, talc, and other particulate matter.
• Birefringent debris frequently are scattered throughout the slide and should not be
mistaken for crystals.
• Birefringent material in the specimen appears as a bright yellow or blue color in
the red field generated by the first-order compensator
• yellow when oriented parallel to the axis of the compensator are negatively
birefringent, and those that are blue are positively birefringent.

12. US finding
• Hyperechoic deposition on the surface of
the articular hyaline cartilage, namely, a
double contour sign, suggested gout with a
sensitivity of 36.8% and a specificity of
97.3%
The characteristic US appearance of a tophus
includes an anechoic halo and hyperechoic
heterogeneous center [16] (Figure 5). The
peripheral anechoic halo likely represents the
fibrovascular zone

13. DECT
• Dual energy X-ray tubes at 80 kv and 140 kv
are placed at 90 degrees to each other and
to their two detectors.
• Based on the spectral dual energy
properties, aggregates of urate crystals can
be uniquely color coded,
• high clinical suspicion of tophaceous gout, in
whom conventional diagnostic tests have
been inconclusive

14. Treatment
• Acute flare – colchicine ( low dose ), NSAIDs, or glucocorticoids (oral –
short course , intraarticular, or intramuscular) as appropriate firstline
therapy for gout flares over IL-1 inhibitors or adrenocorticotropic
hormone (ACTH) is strongly recommended

15. ULT
• Not to start in hyperuricemia
• To be started in gout attacks >2 /year , any tophus or Xray changes
• For first attack with CKD / high UA – ULT can be started
• Allopurinol better choice even in moderate CKD
• Starting with low dose with subsequent titration is recommended
• Concomitant propylaxis is strongly recommended
• Testing for the HLA–B*5801 allele prior allopurinol is conditionally
recommended for patients of Southeast Asian descent (e.g., Han Chinese,
Korean, Thai) and for African American patient
• Treat to target approach , UA < 6

16. Follow facts
• Vegetables are risk factors for gout
• Hyperuricemia mean gout
• Allopurinol use cause AHS always
Avoid myths
• Lifestyle modification needed
• Never overuse NSAIDs
• Weight loss / limited alcohol
/limited high fructose corn syrup/
limited purine
• Adequate treatment when
indicated

17. Case 5
• Elderly male presented with intermittent flares of right knee arthritis 1 year and polyarthritis – 1 month.
• synovial fluid for crystals negative,
• x-ray knee shows – chondrocalcinosis, multiple loose bodies,
• X-ray hand – triangular ligament calcification.

18. Case 6
• 72 year old male non diabetic, non-hypertensive, occasional alcoholic came to the
hospital in EC – IV.
• He was symptomatic since 2 months which initially began with high grade fever abd
decreased by 2 days and began recurrent 1 week later and at this time he had sudden
onset pains initially in b/l ankles and then involved both small and large jui9nts of upper
and lower limbs. He also noted at both the ankles
• gout with age related chondrocalcinosis
• X-Ray Knee → B/L chondrocalcinosis +, osteophyte
• X-Ray hands → Right triangular / calcification+
• X-Ray Pelvis: Chondrocalcinosis at B/L inferomedial margin of hip joint

19. CPPD
• The clinical presentation of CPDD is broad and ranges from an acute monoarticular inflammatory arthritis to a chronic
polyarticular noninflammatory arthritis.
• CPDD can be sporadic or familial , associated with hyperparathyroidism, hemochromatosis, hypophosphatasia, and
hypomagnesemia.
• Accurate diagnosis of CPDD relies on the observation of calcium pyrophosphate crystals in synovial fluid from
affected joints under compensated polarized light microscopy.
• This pathogenesis of CPDD is rooted in excess accumulation of pyrophosphate in hyaline cartilage and fibrocartilage.
• Acute CPP crystal arthritis is managed with strategies similar to those of acute gout, and similar treatments are often
used in patients with the chronic polyarticular forms of CPDD

20. CDS
• Crowned dens syndrome is a distinctive presentation of spinal CPPD
caused by inflammation from CPP crystal deposits around the dens.34
Affected patients have acute neck pain associated with fever, occipital
headache, limited range of motion of the cervical spine, and elevated
inflammatory markers. It may be confused with aseptic meningitis,
tumor, or acute spinal cord compression

22. Chondrocalcinosis

23. CPPD crystal
• Smaller, rhomboid-shaped objects that are weakly positively
birefringent
• It is important to examine all areas of the specimen on the
microscope slide, and possibly to prepare a second wet mount to
exclude or confirm this diagnosis.

26. Case 4
• 77-year-old man known hypertensive, nondiabetic
• Twenty years history of inflammatory polyarthritis,
• Multiple subcutaneous nodules over both elbows and large cystic swelling
over right elbow. IgM-Rheumatoid factor (ELISA) was high titer positive.
• Hand radiography showed erosion in left ulnar styloid process and right
intercarpal joints.
• US- multiple rheumatoid nodules with olecranon bursitis over right elbow,
radiocarpal and intercarpal joint synovitis with lunate erosion.
• The aspirate fluid from olecranon bursa revealed cholesterol crystals which are
characterized by broad plates with broken edge (notched corner)
• Step ladder pattern appearance with intense birefringence on polarizing
microscopy

27. BCP crystal
• Hydroxyapatite can be detected in synovial
fluid, but because these crystals are generally
nonbirefringent, it is not possible to detect
them by polarized microscopy.
• A useful and rapid method is to stain the fluid
with alizarin red S stain and look for clumps
of crystals under routine light microscopy
(Figure 53-4)

28. Milwaukee
shoulder Periarticular or intra-articular deposition of hydroxyapatite or
basic calcium phosphate (BCP) crystals.
While primarily associated with the shoulder joint,
it can affect any joint in the body below the head.
Marked erosion of the humeral head, cartilage, capsule,
and bursae.
Though rare, it is most often seen in females beginning in their
50s or 60s.
Patients often have a history of joint trauma or overuse, CPPD ,
neuroarthropathy, dialysis-related arthropathy or denervation.

29. Others
• Synovial cholesterol crystals appear as flat,
platelike structures with notched corners
• lipid crystals have the appearance of
Maltese crosses.
• strongly birefringent, both negatively and
positively
• Corticosteroid crystals can be highly
birefringent and mimic urate or CPPD
crystals.