Calcinosis: Causes, Symptoms, and Treatment

Calcification is the deposition of calcium salts (usually hydroxyapatite) in soft tissues: skin and subcutaneous tissue, muscles and fascia, and sometimes around joints or in the walls of small arteries. It is not a single disease, but a phenotype that occurs in various conditions, from rheumatological ones (scleroderma, dermatomyositis) to calcium-phosphorus metabolism disorders and chronic kidney disease. For safe management, it is important to first determine the type of calcification and the underlying mechanism before choosing a treatment. [1]

Classically, calcinosis cutis is distinguished with subtypes (dystrophic, metastatic, idiopathic, iatrogenic), tumorous calcinosis (large periarticular masses; often hereditary in hyperphosphatemia) and calciphylaxis - a severe, painful form of calcifying uremic arteriolopathy in patients with end-stage renal failure/dialysis. These forms are treated differently, and this is the key idea of the entire article. [2]

Symptoms and how they differ by type

• Cutaneous (dystrophic) calcinosis in systemic scleroderma/dermatomyositis: dense/crunchy nodules or plaques, most often on the fingers/elbows/knees/buttocks; may rupture, releasing whitish "crumbs," become painful, ulcerate, and interfere with hand function. In systemic scleroderma, the "target" is the hands and fingers. [3]
• Tumorous calcinosis: large, painless or painful "spherical" masses around large joints (hip, shoulder), limited mobility, recurrence after removal. Often familial and persistent hyperphosphatemia. [4]
• Calciphylaxis: acutely painful purplish spots/nodules with rapid necrosis of the skin and subcutaneous tissue (thighs, abdomen, buttocks), serious wound infections. This is an emergency with a high mortality risk and requires immediate multidisciplinary management. [5]

Why it occurs: a brief overview of the mechanisms

• Dystrophic calcinosis: calcium "settles" on damaged tissues with normal calcium and phosphate levels in the blood (chronic inflammation/ischemia in scleroderma, dermatomyositis, trauma). Therefore, treatment often includes control of the underlying disease plus local/procedural methods. [6]
• Metastatic calcification: in systemic imbalances (hyperphosphatemia, hypercalcemia, CKD-MBD in dialysis patients), sedimentation is multiple and "widespread." The key here is to normalize the calcium-phosphorus-PTH ratio. [7]
• Hyperphosphatemic tumoral calcinosis (hereditary): FGF23 deficiency/resistance (FGF23, GALNT3, KL mutations) → kidneys excrete little phosphate → high phosphate and massive periarticular deposits. Treatment is by reducing phosphate (diet + phosphate binders), sometimes acetazolamide/niacinamide, plus surgery if indicated. [8]
• Calciphylaxis: calcific arteriolopathy in patients with CKD/dialysis; risks include high Ca×P product, hyperparathyroidism, warfarin, protein deficiency, and inflammation. The mainstay of treatment is metabolic correction, elimination of triggers, and sodium thiosulfate with aggressive wound and pain management. [9]

Diagnostics: What to take and what to show in the images

1. Laboratory: calcium, phosphate, creatinine/SCF, PTH, alkaline phosphatase, 25(OH)D; if rheumatic background is suspected - ANA, anti-centromere, anti-PM/Scl, etc.; with JDM/DM - myositis panels. If hereditary tumor calcinosis is suspected - persistent hyperphosphatemia and genetics (FGF23/GALNT3/KL). [10]
2. Visualization: X-ray - typical dense shadows; ultrasound - hyperechoic foci with shadows; CT shows the volume and relationship to tendons/vessels; in calciphylaxis, biopsy (examination of vascular calcifications) helps, but the decision is clinical - treatment cannot be delayed until histology. [11]
3. Complication assessment: in cutaneous calcinosis - ulcers/infections, in tumorous calcinosis - joint/nerve compression, in calciphylaxis - wound infection/sepsis. This affects the urgency of interventions. [12]

Treatment: general principle and “branching” by types

The main rule: treat the cause and mechanism, adding topical and procedural methods. No single "anti-calcinosis" drug works equally well for everyone, and the evidence base is often based on case series and reviews. Below is a summary of what is actually used today and where there is support in the modern literature.

1) Dystrophic calcinosis of the skin (scleroderma, dermatomyositis)

• Basic: protection from trauma/cold, active treatment of Raynaud's phenomenon and ulcers, control of the underlying autoimmune disease (in DM/JDM - systemic immunosuppression according to standards; there is increasing but still limited experience with JAK inhibitors in refractory calcinosis in JDM). [13]

• Rheumatologists often use diltiazem, colchicine, and minocycline as first-line treatments: they are inexpensive and have the most “field” experience; the effect is moderate, but the safety is acceptable. [14]

• Sodium thiosulfate (NT):

  • Topical/intralesional 25% - for ulcerative/painful lesions; there are series with a reduction in pain and size of lesions. [15]
  • Systemic (IV) - as an adjuvant when local measures are ineffective; data are retrospective, but show benefit in some patients. Nausea and metabolic acidosis may occur; monitoring is necessary. [16]

• Procedural methods:

  • CO₂/erbium laser, ultrasonic "needling"/ultrasound-guided drilling - for superficial lesions on the fingers.
  • Extracorporeal shock wave therapy (ESWT) - may reduce pain/ulcers in scleroderma-calcinosis (small studies). [17]
  • Surgical removal is targeted, for single “interfering” nodes; there is a high risk of recurrence, so carefully select candidates. [18]

• In the “reserve” for cases: bisphosphonates, rituximab, intravenous immunoglobulin (IVIG) - evidence is mixed; the decision is individual in an experienced center. [19]

2) Tumorous calcinosis (especially familial hyperphosphatemic)

• Goal #1 - Reduce phosphate: phosphate-restricted diet + calcium-free phosphate binders (sevelamer, lanthanum, etc.). Niacinamide/nicotinamide and/or acetazolamide are considered to enhance phosphate excretion - as prescribed individually. [20]
• Genetic verification (FGF23, GALNT3, KL) is important for prognosis and family counseling; experience with the use of targeted molecules is limited, the standard is phosphate monitoring and surgery if indicated (symptomatic masses/compression). [21]

3) Calciphylaxis (calcifying uremic arteriolopathy)

• Emergency multidisciplinary care: nephrologist, dermatologist/wound surgeon, pain anesthesiologist, nutritionist. [22]
• Immediate correction of factors: discontinuation of warfarin, calcium-containing phosphate binders, excessive doses of active vitamin D and/or iron; correction of Ca×P product and PTH (sometimes partial parathyroidectomy), optimization of dialysis; hyperbaric oxygenation is considered as an aid to healing. [23]
• Sodium thiosulfate (IV) is the standard adjuvant (despite the lack of large RCTs, extensive clinical experience has been accumulated); oral regimens are possible for those who cannot receive IV, but the evidence is less robust. Concurrent treatment includes aggressive wound care, antibacterial therapy as indicated, and adequate pain relief. [24]

Table 1. What kind of calcification is in front of us and what to do first

Type	Tips	First steps
Dystrophic cutaneous (scleroderma/DM)	Nodules/plaques on fingers/elbows; normal Ca and P	Treat underlying disease, tissue protection; diltiazem/colchicine/minocycline; topical/intralesional. NT 25%; consider laser/ESWT/acute surgery [25]
Tumorous (periscarious, periarticular)	Large masses around large joints; often hyperphosphatemia	Low phosphate diet + phosphate binders (no calcium); genetics (FGF23/GALNT3/KL); symptomatic surgery [26]
Calciphylaxis	Severe pain + purpura/necrosis in a patient with CKD/dialysis	Urgently discontinue triggers (warfarin, Ca-binders), normalize Ca×P and PTH, intravenous sodium thiosulfate, wound care, pain, consider HBO [27]

Table 2. Drugs and methods for cutaneous calcinosis: what is known

Approach	Where is it used?	What does literature say?
Diltiazem / colchicine / minocycline	Scleroderma/DM	Often used as first line due to availability and safety profile; effect is modest but reproducible in the clinic.[28]
Sodium thiosulfate 25% (topical/intralesional)	Ulcerative/painful lesions	Small series/cases show reduction in pain and size; suitable for “superficial” lesions. [29]
Sodium thiosulfate systemically	Refractory cases	Retrospective data: may be a useful adjuvant; requires monitoring for side effects. [30]
ESWT	Painful lesions in SSc	Small studies: ↓pain/ulcers; center of excellence option. [31]
Laser/surgery	Superficial/limited nodes	Good for "nuisance" lesions; risk of recurrence - discuss with patient. [32]
IVIG/rituximab/bisphosphonates	SSc/DM refractors	Mixed data, point solutions in special centers. [33]

Frequently Asked Questions (FAQ)

• Is it possible to “dissolve” calcification with pills?

There is no single "dissolving" pill. Combinations (diltiazem/colchicine/minocycline + topical sodium thiosulfate) are helpful for cutaneous calcinosis; phosphate reduction is helpful for tumorigenic calcinosis; and calciphylaxis is treated with multi-component treatment of the underlying causes + sodium thiosulfate. [34]

• Is sodium thiosulfate the "standard"? How is it administered?

For calciphylaxis, intravenous NT is a common adjuvant with real clinical benefit; for cutaneous calcinosis, a topical/intralesional 25% solution is more often used, with systemic administration as a reserve. Oral regimens have been described, but the evidence is lower. [35]

• Does tumorous calcinosis always require surgery?

No. Phosphate levels are monitored first (diet + binders), and only then is the question of selective surgery for painful/compressive masses decided. Genetic verification (FGF23/GALNT3/KL) helps with prognosis. [36]

• Are there any "new" treatments for dermatomyositis calcinosis?

For refractory cases, JAK inhibitors (off-label) are being discussed - encouraging series have accumulated, especially in JDM, but there are no RCTs yet; decisions lie in experienced centers. [37]

• Should warfarin be discontinued in case of calciphylaxis?

Yes, this is one of the standard measures (switching to an alternative anticoagulant, most often apixaban), along with correction of Ca×P/PTH, intensification of dialysis, wound care, consideration of hyperbaric oxygenation and the appointment of NT. [38]