Calcinosis: Symptoms, Types, Causes and Treatment

Calcinosis is a complex and often challenging condition characterized by abnormal calcium deposits in the skin, subcutaneous tissues, and sometimes deeper structures like muscles or organs. It can be a source of significant discomfort, pain, and disability, especially when linked to underlying diseases such as systemic sclerosis or inherited metabolic disorders. This article offers a comprehensive look at calcinosis, exploring its symptoms, the various types, underlying causes, and available treatment strategies, supported by evidence from recent research.

Symptoms of Calcinosis

Calcinosis may present subtly or be dramatically apparent, depending on the extent and location of calcium deposits. Recognizing the symptoms is crucial for early diagnosis and intervention, especially in patients with autoimmune or metabolic diseases.

Symptom	Description	Impact	Source(s)
Pain	Localized discomfort, often at hands/joints	Reduces quality of life	2 7 14
Skin Ulcers	Open sores over calcified areas	Risk of infection, pain	1 7 9
Tenderness	Sensitivity over deposits	Functional limitation	2 7
Lump/Mass	Palpable or visible nodules/masses	Cosmetic, functional issues	2 5 7
Extrusion	Calcium breaking through skin	Infection risk, discharge	2 7
Disability	Impaired hand or joint function	Daily living limitations	2 7 9 14

Table 1: Key Symptoms

Pain and Tenderness

Pain is a dominant symptom, frequently reported in areas where calcium deposits form, particularly in the hands and around joints. Tenderness may accompany pain, making simple tasks like gripping difficult and uncomfortable 2 7 14.

Skin Ulcers and Extrusion

Skin ulcers—open sores that develop over calcified areas—are a common and troublesome complication. In some cases, the calcium deposits spontaneously extrude through the skin, leading to discharge and increasing the risk of secondary infection 1 2 7 9.

Nodules, Masses, and Cosmetic Changes

Calcinosis often manifests as palpable lumps or masses beneath the skin. These can be small and localized or, in rare cases, form large, tumor-like growths (as in tumoral calcinosis) around joints. Such masses can affect appearance and restrict joint movement, contributing to disability 2 5 7.

Functional Disability

The presence of calcinosis, especially in the hands, significantly impairs function. Patients may struggle with daily activities such as dressing, writing, or handling objects. This functional loss can be profound, especially when multiple locations are involved 2 7 9 14.

Types of Calcinosis

Calcinosis is not a single disease but a spectrum of disorders. Understanding its subtypes helps guide diagnosis and management.

Type	Main Features	Common Causes/Associations	Source(s)
Dystrophic	Normal serum calcium/phosphate, local tissue damage	Autoimmune/connective tissue diseases	3 9 14
Metastatic	Elevated serum calcium/phosphate	Chronic kidney disease, hyperparathyroidism	3 6
Idiopathic	No clear cause or metabolic disturbance	Sporadic, rare	3
Iatrogenic	Medication/therapy induced	Medical procedures, infusions	3
Calciphylaxis	Vascular calcium deposition, severe skin necrosis	Renal failure, hyperparathyroidism	3
Tumoral Calcinosis	Large periarticular masses, familial or secondary	Genetic mutations, renal disease	4 5 6 8 10 11

Table 2: Types of Calcinosis

Dystrophic Calcinosis

This is the most common subtype, occurring when calcium is deposited in areas of damaged or inflamed tissue, despite normal blood calcium and phosphate levels. Dystrophic calcinosis is often seen in autoimmune disorders like systemic sclerosis, dermatomyositis, and lupus 3 9 14.

Metastatic Calcinosis

Unlike dystrophic calcinosis, metastatic calcinosis results from abnormal mineral metabolism—typically high levels of calcium and/or phosphate in the blood. It is often associated with chronic kidney disease, hyperparathyroidism, or other metabolic disturbances 3 6.

Idiopathic Calcinosis

In this rare form, calcium deposits occur without any identifiable underlying disease or metabolic abnormality. The cause remains unknown, and cases are usually sporadic 3.

Iatrogenic Calcinosis

This type is induced by medical interventions, such as repeated calcium-containing infusions or certain medications, leading to local calcium deposition in the skin or soft tissues 3.

Calciphylaxis

Calciphylaxis is a severe, life-threatening form characterized by calcium deposition in the blood vessels of the skin and subcutaneous fat, leading to skin necrosis. It is most commonly associated with advanced renal failure and secondary hyperparathyroidism 3.

Tumoral Calcinosis

Tumoral calcinosis is a rare condition, often inherited, characterized by massive, lobulated calcified masses around large joints (like the hips and shoulders). It can be familial (primary) due to genetic mutations or secondary to metabolic disturbances such as chronic renal failure 4 5 6 8 10 11.

Causes of Calcinosis

The underlying causes of calcinosis are diverse, ranging from local tissue damage to complex genetic mutations affecting mineral metabolism.

Cause	Description	Associated Conditions/Mechanisms	Source(s)
Tissue Injury	Damage from inflammation or trauma	Autoimmune disease, mechanical	3 9 14
Metabolic Abnormalities	High serum calcium/phosphate	Renal failure, hyperparathyroidism	3 6 15
Genetic Mutations	Affecting phosphate metabolism	Tumoral calcinosis (GALNT3, FGF23, KLOTHO)	5 6 8 10 11
Autoimmunity	Immune-mediated tissue damage	Systemic sclerosis, dermatomyositis, lupus	1 2 3 9 14
Iatrogenic	Medical interventions	Infusions, injections	3

Table 3: Causes of Calcinosis

Tissue Injury and Inflammation

The most frequent cause, particularly in dystrophic calcinosis, is local tissue injury—often due to inflammation from autoimmune disorders or trauma. Chronic inflammation damages tissues, creating a nidus for calcium deposition even when serum calcium and phosphate remain normal 3 9 14.

Metabolic Disturbances

Metastatic calcinosis arises in the context of abnormal mineral metabolism. Chronic kidney disease is a major risk factor, as it can lead to hyperphosphatemia and secondary hyperparathyroidism, both of which promote calcium phosphate precipitation in tissues 3 6 15.

Genetic Factors

Certain rare forms, such as familial tumoral calcinosis, are caused by inherited mutations in genes that regulate phosphate handling—most notably GALNT3 and FGF23. These mutations lead to excessive phosphate reabsorption in the kidneys, resulting in hyperphosphatemia and massive periarticular calcium deposits 5 6 8 10 11.

Autoimmune Diseases

Autoimmune connective tissue diseases (systemic sclerosis, dermatomyositis, lupus) are strongly associated with dystrophic calcinosis. The immune system attacks the body’s own tissues, producing chronic inflammation and subsequent calcium deposition 1 2 3 9 14.

Iatrogenic Causes

Medical interventions, including repeated calcium-based infusions or certain medications, can induce calcinosis. This is termed iatrogenic calcinosis and is usually preventable with careful monitoring 3.

Treatment of Calcinosis

Managing calcinosis is challenging due to the lack of standardized, highly effective treatments. Approaches are often individualized, combining medical, physical, and surgical strategies.

Treatment	Approach/Method	Evidence/Usefulness	Source(s)
Medical Therapy	Diltiazem, bisphosphonates, minocycline, colchicine, sodium thiosulfate	Varying benefit, limited trials	12 13 14 16
Biologic Therapy	Rituximab, TNF inhibitors	Promising for autoimmune calcinosis	13 16
Physical Methods	Laser, extracorporeal shock wave	Useful for superficial lesions	12 13 14 16
Surgical Excision	Removal of calcified masses	For severe/disabling cases	12 13 14 16
Phosphate Binders/Diet	Phosphate restriction, binders	For tumoral/secondary calcinosis	6
Parathyroidectomy	Surgical removal of parathyroid	Severe secondary calcinosis	6

Table 4: Treatment Options

Medical Therapies

• Diltiazem & Bisphosphonates: Calcium channel blockers like diltiazem and bone metabolism regulators such as bisphosphonates have shown some benefit, particularly in autoimmune-related calcinosis. Evidence is limited, but these agents may reduce calcium deposition or slow progression 12 13 14 16.
• Minocycline & Colchicine: Both drugs have anti-inflammatory properties and anecdotal reports of efficacy in reducing calcinosis lesions, especially in connective tissue disease 12 13 14.
• Sodium Thiosulfate: Topical or intralesional sodium thiosulfate is emerging as a potential therapy, particularly for localized calcinosis 13 14.

Biologic and Immunomodulatory Therapy

• Rituximab: This monoclonal antibody, used to suppress autoimmune activity, has shown promising results in systemic sclerosis and dermatomyositis-associated calcinosis 13 16.
• TNF Inhibitors: Particularly in juvenile dermatomyositis, TNF inhibitors may help reduce calcinosis, though evidence remains preliminary 13.

Physical and Surgical Approaches

• Laser and Shock Wave Therapy: Carbon dioxide laser vaporization and extracorporeal shock wave lithotripsy can help break down or remove superficial deposits, improving symptoms and appearance 12 13 14 16.
• Surgical Excision: When calcinosis causes severe pain, ulcers, or functional impairment, surgical removal is sometimes necessary. However, recurrence is common, especially if the underlying cause is not controlled 12 13 14 16.

Metabolic Management

• Phosphate Binders and Dietary Restriction: For tumoral calcinosis and secondary (metabolic) calcinosis, lowering phosphate intake and using binders can be effective first-line options 6.
• Parathyroidectomy: In patients with calcinosis due to severe secondary hyperparathyroidism (often from chronic kidney disease), surgical removal of the parathyroid glands may be required 6.

Limitations and Research Gaps

There are currently no universally effective treatments for calcinosis, and most evidence comes from case reports or small case series. Larger, controlled studies are needed to establish best practices 12 13 14 16.

Conclusion

Calcinosis is a multifaceted condition that can significantly impact quality of life, especially for those with underlying autoimmune or metabolic disorders. Recognizing the symptoms, understanding the types and causes, and staying informed about evolving treatment options are key for patients and clinicians alike.

Main Points Covered:

• Calcinosis presents with pain, tenderness, skin ulcers, nodules, and functional disability, particularly in the hands and around joints 2 7 9 14.
• Several types exist, including dystrophic, metastatic, idiopathic, iatrogenic, calciphylaxis, and tumoral calcinosis—each with distinct causes and implications 3 4 5 6 8 9 10 11 14.
• Causes range from tissue injury and autoimmunity to metabolic disturbances and genetic mutations affecting phosphate metabolism 1 2 3 5 6 8 9 10 11 14.
• Treatment remains challenging, with options including medical therapies (diltiazem, bisphosphonates, minocycline, sodium thiosulfate), biologic agents (rituximab), physical methods (laser, shock wave), surgical removal, and metabolic management for specific subtypes 6 12 13 14 16.
• Ongoing research and clinical trials are needed to find more effective, standardized treatments for calcinosis.

Staying informed and working with a multidisciplinary healthcare team can help patients manage this complex disorder and improve their quality of life.