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Crystalline Diseases

Contributor: Santhanam Lakshminarayanan, MD

CASE 1:

A 78 year old man is seen in the clinic for a painful swelling of the left elbow. Over the past year, he has had a few episodes of pain and swelling in his right knee and left foot, for which he received ibuprofen and once was treated with an antibiotic. His elbow is shown in the picture. He also has hypercholesterolemia and hypertension and is on simvastatin, hydrochlorthiazide and metoprolol.

He drinks a couple of beers a day but does not smoke.

His exam was remarkable only for the appearance of his hands similar to the picture shown.

His labs reveal: (normal ranges)

WBC 11.4/cu mm (4-10/cu mm).

Hb 13.5 g/dL (11-14g/dL).

Platelets 96/cu mm (150-450/cu mm)

AST 65 U/L (20-45 U/L)

ALT 64 U/L (20-45 U/L)

Creatinine 1.7 mg/dL (0.6-1.2 mg/dL)

ESR 86mm/hr

What is the most appropriate next step, respectively?

  • Aspiration of the olecrenon bursa was done.  Findings under polarized microscopy showed the presence of intracellular negatively birefringent crystals. Treatment consisted of injection of steroids (in the absence of an obvious infection) into the olecrenon bursa.  In addition to intra-articular injections, other treatments for acute gout include NSAIDs, colchicine, and oral gluccocorticoids. Urate lowering therapy is almost never initiated during an acute attack.  If a patient is already on urate lowering therapy or it was briefly interrupted, it should be continued or restarted.

Having established the diagnosis and provided relief for the acute problem what are the next steps in the management of this patient?

  • The patient's serum uric acid level needs to be documented once the acute episode has resolved completely, as it is not uncommon for the serum uric acid level to be normal during an acute attack of gout. The patient's risk factors for hyperuricemia need to be addressed: alcohol intake (his intake is significant and may be a cause for his thrombocytopenia), and medications (hydrochlorthiazide) as well as lifestyle and dietary issues.
  • Gout treatment is predicated upon comorbid conditions.  His renal function is suboptimal and would impact some treatments you may offer, including NSAIDs, which can adversely affect renal function, colchicine, which can lead to myelosuppression in renal insufficiency and urate lowering therapies such as allopurinol or febuxostat, which although not directly toxic to the kidney, needs to be dose titrated with respect to renal insufficiency. Febuxostat does not require dosage adjustment for a creatinine clearance greater than 30 cc/min. Dosing is not defined for creatinine clearance below 30 cc/min.
  • In general, once urate lowering therapy is initiated with allopurinol or febuxostat, prophylactic therapy with NSAIDS, colchicine or glucocorticoids is continued for approximately six months, to prevent flares commonly seen during initial urate lowering therapy.
  • Colchicine can cause significant diarrhea and should almost never be dosed in the "traditional" way of 0.6 mg every 2 hours for 6 doses or until the patient has diarrhea. It can be efficacious in twice daily dosing. Intravenous colchicine is no longer available.
  • The serum uric acid level should be monitored regularly during treatment, with dose titration until a target goal of less than 6.0 mg/dL is achieved.

CASE 2:

You are asked to see an elderly lady admitted to the hospital for pneumonia 4 days ago. She has a painful swollen wrist with no antecedent history of a fall. The hospitalist team did an x-ray of the wrist and hand. The wrist is minimally warm and tender with some decreased range of motion secondary to pain. The pneumonia is improving and she was looking forward to being discharged on oral antibiotics. She mentioned that she had bumped her knee on the dresser on the day of admission and had an X-ray.

What is your diagnosis?

The presentation and x-ray findings are typical for acute crystalline arthritis secondary to calcium pyrophosphate dihydrate deposition. The typical locations for chondrocalcinosis are the triangular fibrocartilage in the wrist and the menisci and articular cartilage in the knee. The clinical scenario of a patient hospitalized for an acute illness developing an acute inflammatory arthritis should include both gout, pseudogout (CPPD) and septic arthritis in the differential. Aspiration of the synovial fluid is vital in establishing a diagnosis.  If the index of suspicion for infection is high, then the mere presence of crystals, especially if extra cellular should not lead one to discount septic arthritis as the two conditions can co-exist (1, 2). In this lady, she feels well enough to want to go home and the usual hallmarks of a septic joint: very warm, acutely tender with guarding against any range of motion, fever and toxic appearance are absent. The caveat is that she is elderly and received antibiotics for her pneumonia, which may alter the clinical picture and culture results.

What is the most appropriate intervention?

Aspiration of the synovial fluid in the wrist for analysis, and intra-articular Injection of steroids (in the absence of any obvious infection). The fluid may show weakly positively bi-refringent crystals.

What chronic management is indicated?

CPPD is common in older individuals, especially with osteoarthritis.  In younger people, a work-up for secondary causes of CPPD is indicated.  Therefore, screening for hemochromatosis, hypothyroidism, hyperparathryoidism and disorders of magnesium and phosphatase are indicated.  In the absence of a secondary cause, chronic intervention is usually not needed, or very effective.

Patient care

  1. Be able to identify the salient features of an acute arthritis and come up with a differential diagnosis based on features in the history and physical examination.
  2. Recognize the importance of ruling out septic arthritis in the process of evaluating an acute Monoarthritis.
  3. Recognize the importance of a joint aspiration and synovial fluid analysis in making the diagnosis.
  4. Describe the importance of pain relief in the setting of an acute Monoarthritis.
  5. Be able to ascertain the epidemiology and trigger factors in gout and CPPD in a given patient and counsel them regarding the same.
  6. Describe the laboratory and radiographic investigations that may be helpful in supporting the diagnosis of gout and CPPD and also understand their shortfalls.
  7. Know the medications used in the acute and chronic management of gout (1, 2) and CPPD and be able to explain the potential side effects.
  8. Describe the course of these conditions and their co-morbid disease associations (1, 2).
  9. Describe two types of calcium crystals that can lead to arthropathy.

Medical Knowledge

  1. Know the purine metabolism pathway and the steps affected by urate lowering therapy and logically explain potential drug interaction and toxicities
  2. Know the clinical presentation of gout and Pseudogout and be able to recognize the pattern of classic joint involvement and distinguishing clinical features of an inflammatory arthritis.
  3. Describe the role of inflammation in gout.
  4. Know the classic locations for a gouty tophus (1, 2, 3)
  5. Know the crystals involved and be able to recognize them under polarized microscopy (1, 2, 3, 4).
  6. Know the similarities and differences in synovial fluid analysis in acute crystal arthropathy and septic arthritis
  7. Know the role of the kidney in urate transport
  8. Know the radiological features of gout and Pseudogout (1, 2, 3, 4, 5, 6).
  9. Know the mechanism of action of the various pharmacological interventions and their side effects and drug- drug interactions.
  10. Describe when to initiate therapy with urate lowering therapy and the risks of potentially inducing a flare upon such initiation.  Describe how to prevent flares associated with urate lowering therapy.
  11. Know the real and important distinction between gouty arthropathy and asymptomatic hyperuricemia especially in the setting of concurrent hydrochlorothiazide therapy
  12. Know also that gouty arthropathy is but one aspect of the gouty diathesis.
  13. Understand the importance of appropriate corticosteroid use
  14. Know the recent advances in pharmacotherapy of gout

Interpersonal and communication skills

  1. Be able to clearly anatomical and accepted medical terms describe the patients presentation assuming that the attending physician can see neither you nor the patient and is on the other end of the phone
  2. Be able to clearly and in lay terms explain the diagnosis and plan of care to the patient
  3. Counsel patient clearly on lifestyle issues as they impact on the disease
  4. Explain the need for compliance in the setting of a chronic condition
  5. Educate patient regarding the co-morbid conditions associated with gout and help screen as appropriate
  6. Explain the potential side effects of planned treatments and plan for monitoring for the same
  7. Recognize the need to include the patient's perspectives in the treatment of this life-long disease.

Professionalism

  1. Be an educated patient advocate
  2. Respect patient privacy and discuss all patient related issues with honesty and integrity
  3. Respect the patients' right to refuse treatment
  4. As a corollary respect your right as the physician to lay out a clear plan and expect an attempt at compliance
  5. Show empathy.

Problem-based learning

  1. Have a mechanism to seek and incorporate feedback from patients and attending physicians into your practice
  2. Learn from your mistakes and incorporate changes into your practice to prevent errors in the future.
  3. Have resource/resources you go to for refreshing knowledge base- textbook, web resources or journal articles

Systems based practice

  1. Recognize barriers to the institution of your plan of care for the individual patient- medical, psycho-social, economic or cultural
  2. Be able to deliver the care needed in a multi-disciplinary settin
  3. Understand the impact of the interventions both in medical terms and in economic terms

Keywords: Gout, Pseudogout, Calcium Pyrophosphate Deposition, Crystalline Arthropathy, Basic Calcium Phosphate Crystal

References