Treatments for CPPD with mechanism of action, adverse effects, and supporting evidence
| Therapy | Indication (acute vs. chronic CPP crystal arthritis) | Mechanism | Adverse effects | Examples of literature supporting use in CPPD |
|---|---|---|---|---|
| Rest and ice pack application | Acute | Reduces blood flow and therefore inflammation in the affected area | None known | EULAR recommendations (Zhang et al. [6]), literature on gout |
| Joint aspiration | Acute | Relieves pressure on the distended joint capsule | Septic arthritis, bleeding, neurovascular or tendon damage, others (rare) | EULAR recommendations (Zhang et al. [6]), a small study (O’Duffy [15]), literature on gout |
| Intra-articular glucocorticoid injection | Acute | Locally alters gene expression in a way that has anti-inflammatory effects | Septic arthritis, bleeding, neurovascular or tendon damage, post-injection flare, local skin or fat changes, osteonecrosis, allergy, others (rare) | EULAR recommendations (Zhang et al. [6]), a small study (O’Duffy [15]), literature on gout |
| Oral NSAIDs (with gastroprotection) | Gastrointestinal (ulcer, bleeding, dyspepsia), renal (hypertension, edema, electrolyte disturbance, AKI), cardiovascular, pulmonary, hematologic, hepatic, anaphylaxis or allergy, drug interactions | EULAR recommendations (Zhang et al. [6]), literature on gout | ||
| Oral colchicine | Diarrhea, nausea, vomiting, neuromyopathy, toxicity (cytopenia, liver failure, rhabdomyolysis) | EULAR recommendations (Zhang et al. [6]), a small study on prophylaxis (Alvarellos et al. [16]), RCT comparing colchicine to prednisone (Pascart et al. [9]), RCT on dosing (Laosuksri et al. [10]), retrospective cohort (Damart et al. [11]), literature on gout | ||
| Oral or parenteral glucocorticoids | Acute and chronic (lower dose) | Systemically alters gene expression in a way that led to anti-inflammatory effects, activates anti-inflammatory proteins | Endocrine (HPA suppression, hyperglycemia, weight gain), dermatologic (i.e., Cushingoid striae), cardiovascular (hypertension, edema, etc.), gastrointestinal, bone, and muscle (osteoporosis, myopathy, etc.), neuropsychiatric, ophthalmologic (increased intraocular pressure, cataracts, etc.), immune (i.e., immunosuppression), injection site pain, others | EULAR recommendations (Zhang et al. [6]), RCT comparing oral prednisone to anakinra (Dumusc et al. [12]), RCT comparing prednisone to colchicine (Pascart et al. [9]), study comparing parenteral glucocorticoids to diclofenac (Werlen et al. [17]), study on intramuscular triamcinolone acetonide (Roane et al. [18]), retrospective cohort (Damart et al. [11]) |
| ACTH (parenteral) | Acute | Similar to glucocorticoids, hyperpigmentation | Case series (Daoussis et al. [19]), literature on gout (Siegel et al. [20], Axelrod et al. [21]) | |
| Methotrexate (subcutaneous) | Chronic | Inhibition of dihydrofolate reductase, adenosine-mediated effect, others | Folate deficiency, myelosuppression, teratogenicity and toxicity, pulmonary, injection site pain, others | EULAR recommendations (Zhang et al. [6]), RCT (Finckh et al. [22]), small observational study (Andres et al. [23]) |
| Hydroxychloroquine (oral) | Chronic | Interferes with lysosomal activity and autophagy by accumulating in lysosomes | Ophthalmic (retinopathy), hematologic (i.e., anemia, aplastic anemia, myelosuppression), cardiovascular (sick sinus syndrome), dermatologic, endocrine (weight loss), gastrointestinal, hepatic, hypersensitivity, neurologic, respiratory | EULAR recommendations (Zhang et al. [6]), RCT (Rothschild and Yakubov [24]), retrospective cohort (Damart et. al [11]) |
| Biologics | Acute and chronic | Antagonize interleukin receptors or neutralize interleukin signaling | Immunosuppression, infections, injection site reactions, etc. | Cohort studies and case series (i.e., Damart et al. [11], Lian et al. [13], Latourte et al. [25], etc.), RCT comparing anakinra to prednisone (Dumusc et al. [12]), retrospective cohort (Damart et al. [11]) |
ACTH: adrenocorticotrophin hormone; CPPD: calcium pyrophosphate deposition disease; EULAR: European League Against Rheumatism; HPA: hypothalamic-pituitary-adrenal axis; RCT: randomized controlled trial; CPPD: calcium pyrophosphate deposition disease; NSAID: non-steroidal anti-inflammatory drug; AKI: acute kidney injury
