Mineral dystrophies of the skin: causes, diagnosis, treatment

Mineral dystrophies of the skin are a group of conditions in which inorganic salts, most often calcium (calcinosis cutis), are deposited in the skin and/or subcutaneous tissue; less commonly, true bone tissue is formed (osteoma cutis), or other crystals accumulate (for example, urate tophi in gout). The key to understanding this group is to distinguish the type of mechanism: dystrophic (due to damaged tissue with normal calcium-phosphorus metabolism), metastatic (due to systemic hypercalcemia/hyperphosphatemia), iatrogenic (after infiltration of calcium-containing drugs), idiopathic (without a clear cause), and a special variant - calciphylaxis (calcifying arteriolopathy) in chronic kidney disease. [1]

In practice, "mineral dystrophies" are not a diagnosis, but a diagnostic framework that requires a step-by-step search for systemic causes: impaired renal function, hyperparathyroidism, drug effects (e.g., warfarin), autoimmune diseases (systemic scleroderma, dermatomyositis), and hereditary defects in phosphate regulation (familial hyperphosphatemic tumor-like calcinosis). Correct classification determines the tactics, prognosis, and choice of therapy—from local methods to systemic drugs, dialysis correction, and surgery. [2]

The evidence base is heterogeneous: for calcinosis cutis, most interventions rely on case series and retrospective studies; for gout and hyperphosphatemia, there are high-quality guidelines and randomized trials. Therefore, below I distinguish between areas where strong recommendations exist (e.g., urate-lowering therapy for tophaceous gout; phosphate-lowering therapy in dialysis patients) and areas where decisions are made individually by a consultation. [3]

Finally, it's important to understand that "calcinosis cutis" and "calciphylaxis" are not synonymous. The former describes calcium deposition in the skin due to different causes; the latter describes an extremely severe vascular arteriolopathy with a high mortality rate, most often in patients on dialysis. The approaches to their management differ fundamentally. [4]

Code according to ICD-10 and ICD-11

In international statistics, calcinosis cutis and associated mineral disorders are most often coded. For everyday dermatological practice, the basic ICD-10 code is L94.2 (Calcinosis cutis). When discussing the metabolic background, block E83.* (disorders of mineral metabolism) is used, including E83.59 ("other disorders of calcium metabolism", which in the indices includes "calcinosis (interstitial/tumorous/universal)") and E83.39 ("other disorders of phosphorus metabolism", used, for example, in hyperphosphatemia). There is no specific separate code for calciphylaxis in ICD-10, but in registries it is often classified under E83.59. [5]

In ICD-11, a separate section EB90.4 "Calcification of the skin and subcutaneous tissue" was created with clarifications: EB90.40 (dystrophic calcification of unspecified etiology), EB90.41 (calcifying panniculitis), EB90.42 (calcifying arteriolopathy - calciphylaxis), EB90.4Y (other specified variants, including calcification in inflammatory skin diseases/scleroderma). This block is convenient for the clinician: it distinguishes between cutaneous calcification and vascular arteriolopathy. [6]

Table 1. ICD codes applicable to mineral dystrophies of the skin

Situation	ICD-10	Comment	ICD-11	Comment
Calcinosis cutis	L94.2	Basic dermatological code	EB90.40 / EB90.4Y	Dystrophic/specified calcinosis
"Calcification" in indices	E83.59	"Other disorders of calcium metabolism" (incl. tumoral/interstitial/universalis)	-	-
Hyperphosphatemia/phosphate disorders	E83.39	Other disorders of phosphorus metabolism	-	In ICD-11 they code according to the endocrine section
Calciphylaxis	(more common) E83.59	There is no specific code in ICD-10	EB90.42	Calcifying arteriolopathy

Epidemiology

The absolute prevalence of calcinosis cutis in the population is unknown; it is predominantly a secondary phenomenon in systemic connective tissue diseases. According to modern reviews, calcinosis is observed in 18-49% of patients with systemic sclerosis (more often with a long course, vascular phenotype, anti-centromere seropositivity), and large series confirm a frequency of approximately 25-30%. In patients with dermatomyositis, it is up to 20% in adults and up to 75% in the juvenile form. [7]

Calciphylaxis is a rare but extremely serious condition in patients with end-stage renal disease. Estimates range from 1 to 35 cases per 10,000 dialysis patients per year; some cases remain undiagnosed. One-year mortality remains high, ranging from approximately 37% in modern cohorts to 60-80% in ulcerative forms, with sepsis being the leading cause of death. [8]

Tumorous calcinosis (including familial hyperphosphatemic calcinosis) is a rare orphan phenotype associated with FGF23 pathway abnormalities (mutations in FGF23, GALNT3, KLOTHO, or autoantibodies to FGF23); it typically begins in childhood/adolescence and presents with large periarticular calcifications. The frequency has not been established; familial clusters have been described. [9]

Cutaneous osteoma (cutaneous ossification) is a rare benign dermatosis-"metaplasia", which occurs as a primary (including associations with genetic syndromes) and secondary at the site of inflammation/scars; isolated pediatric series were published in 2025. [10]

Reasons

Calcinosis cutis occurs either due to local tissue damage (dystrophic mechanism) or against the background of a systemic imbalance of calcium-phosphorus metabolism (metastatic). The first group includes calcinosis in scleroderma, dermatomyositis, chronic ulcers, after injuries, injections, and infections; the second group includes hyperparathyroidism, renal failure with hyperphosphatemia, and hypervitaminosis D. [11]

A special situation is calciphylaxis: medial calcification of small arteries of the dermis/subcutaneous tissue in the setting of CKD-MBD (chronic kidney disease with impaired bone mineral metabolism), with trigger factors (warfarin, high phosphate, high Ca×P product, hyperparathyroidism). This is a vascular catastrophe, not “simple calcification.” [12]

Iatrogenic calcinosis occurs after extravasation of calcium-containing solutions, calcium carbonate/gluconate, phosphate-containing agents, calcium pastes, etc. Idiopathic forms include, for example, scrotal calcinosis; the pathogenesis is controversial (some authors consider it as dystrophic calcification of epidermal cysts). [13]

Hereditary and rare causes include familial hyperphosphatemic tumoral calcinosis (FGF23 deficiency/resistance), progressive ossifying syndromes, and primary cutaneous osteoma associated with genetic defects (eg, GNAS in AHO spectrum variants). [14]

Risk factors

Universal risk factors for cutaneous calcinosis include chronic inflammation/microtrauma, long-standing ulcers, chronic venous stasis, diabetes mellitus, and smoking. For scleroderma, vascular phenotypes and disease duration are significant; for dermatomyositis, severe cutaneous muscle inflammation and juvenile age are significant. [15]

For calciphylaxis - female gender, obesity, diabetes mellitus, hyperphosphatemia, high Ca×P, hyperparathyroidism, albumin deficiency, warfarin intake; some studies mention the role of activated vitamin D and calcium-containing phosphate binders. [16]

For tumoral calcinosis, hyperphosphatemia and genetics of the FGF23 pathway are associated; trauma and stress around joints provoke mass growth. For cutaneous osteoma, preexisting inflammatory processes/scars and, extremely rarely, genetic syndromes with cutaneous ossification. [17]

Table 2. Risk factors by subtype

Subtype	Key factors
Dystrophic calcinosis	Chronic inflammation, autoimmune diseases (SCL, DM), trauma/ulcers
Metastatic calcification	Hyperparathyroidism, CKD-MBD, hypervitaminosis D
Calciphylaxis	Dialysis, hyperphosphatemia, high Ca×P, warfarin, diabetes, obesity
Tumorous calcinosis	Hereditary defects of FGF23/GALNT3/KLOTHO, hyperphosphatemia
Skin osteoma	Local metaplasia at the site of calcifications/scars; less commonly, genetic forms [18]

Pathogenesis

In dystrophic calcification, necrotic/damaged tissues become a matrix for the precipitation of calcium salts (hydroxyapatite/calcium phosphate) with normal serum Ca and P. Barrier defects, inflammatory mediators and reduced availability of pyrophosphate (an endogenous inhibitor of mineralization) are important links. [19]

Metastatic calcification is caused by systemic imbalances: hypercalcemia/hyperphosphatemia, increased Ca×P product; crystals are deposited in the skin and blood vessels. CKD-MBD, hyperparathyroidism, and excess calcium/vitamin D intake are typical scenarios. [20]

Calciphylaxis - medial calcification and thrombosis of dermal/fatty arterioles, ischemia and necrosis. Phosphate levels and FGF23/PTH dysregulation, the effect of warfarin (antagonism of vitamin K-dependent carboxylation of matrix Gla protein - a calcification inhibitor) are considered key mechanisms. [21]

Cutaneous osteoma is ossification (formation of mature bone tissue) in the dermis/subcutaneous tissue through fibroblast metaplasia, sometimes in the focus of previous calcification; in primary forms, associations with genetic disorders (e.g., GNAS) are possible. This distinguishes it from simple "salt deposition". [22]

Symptoms

The clinical presentation varies from hard subcutaneous nodules to painful ulcers with the release of a whitish "sand" (calcium paste). With a superficial location, ulceration, recurrent infections, pain, and limited function due to painful plaques and contractures are possible. The hands, elbows, knees, and shins are common locations in scleroderma; the gluteal regions and around large joints are common in tumorous calcinosis. [23]

Calciphylaxis presents with extremely painful, livedo-like spots/nodes that quickly develop into necrotic ulcers with a black crust, most often on the thighs/abdomen. Systemic symptoms include severe pain and fever with infection. This is an emergency. [24]

In gout, cutaneous mineral deposits are called tophi: dense nodules with flexible coverings, sometimes with fistulization and the release of chalky material; they are associated with arthritis. In cutaneous osteoma, stony papules/plaques appear, sometimes as a cosmetic defect without pain. [25]

Table 3. Clinical clues by subtype

Sign	Dystrophic	Metastatic	Calciphylaxis	Tumorous	Skin osteoma
Pain	±	±	Expressed	+/−	−/±
Ulcers/infections	Often	May be	Very often	Rarely	No
Serum Ca/P	Norm	↑Ca and/or ↑P	Often ↑P	Often ↑P	Norm
Typical zones	Injury sites, hands	Various	Hips/belly	Periarticular	Face, torso, limbs [26]

Classification, forms and stages

The classical clinical and etiological classification of calcinosis cutis includes five types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis (calcifying arteriolopathy). This determines the diagnostic pathway and targeted treatment. [27]

Based on the morphology of the lesions, micro- and macrocalcifications, conglomerates, calcifying panniculitis, and vascular wall calcification (especially in calciphylaxis) are distinguished. Tumorous calcinosis is characterized by large multilocular masses with a fluid-calcium level on CT/MRI. [28]

Staging is most often based on symptoms and risks: 1) asymptomatic solid nodules; 2) painful lesions without ulcers; 3) ulcers/infections; 4) functional impairment; 5) risk of necrosis/sepsis (calciphylaxis). This influences the choice between conservative, minimally invasive, and surgical approaches.

Skin osteoma is divided into primary (including as part of genetic syndromes) and secondary (at the site of vascular, inflammatory, cicatricial processes). [29]

Complications and consequences

The main problems are chronic pain, ulceration and secondary bacterial infection, limitation of function (especially with periarticular calcifications), cosmetic defect, and decreased quality of life. [30]

Calciphylaxis carries a high risk of rapidly progressing necrosis and sepsis, with a mortality rate of up to 60-80% in ulcerative cases. Early diagnosis and multidisciplinary management are critical. [31]

In tumoral calcinosis, mechanical complications (limited movement, compression) and recurrence after removal without phosphate correction are common. In cutaneous osteoma, complications are rare; indications for treatment are most often cosmetic or related to local discomfort. [32]

Table 4. Key complications

Subtype	Main risks
Calcification in SCL/DM	Pain, ulcers, infections, limitation of function
Calciphylaxis	Necrosis, sepsis, high mortality
Tumorous calcinosis	Relapse, limitation of movement
Skin osteoma	Cosmetic defect, rare symptom [33]

When to see a doctor

1. If hard, painless nodules appear in the skin, especially in cases of known autoimmune diseases, a dermatologist/rheumatologist is needed. 2) If very painful spots/nodes develop that turn into a black scab in a patient with chronic kidney disease, see a doctor immediately (suspected calciphylaxis). [34]
2. Recurrent "chalky" discharge from ulcers/fistulas, especially in the context of scleroderma/dermatomyositis - clarification of the type of calcification and tactics is required. 4) In patients with gout with visible tophi - make an appointment with a rheumatologist for systemic urate-lowering therapy, otherwise local measures are ineffective. [35]

Diagnostics

Step 1 - Clinical examination and simple methods. Detailed examination, photographic documentation, dermatoscopy (whitish structures are sometimes visible), plain radiographs/ultrasound of the affected areas (echo-negative/hyperechoic shadows with an acoustic path), for large masses - CT/MRI. [36]

Step 2 - Basic laboratory. Calcium/phosphorus (and Ca×P product), magnesium, PTH, creatinine, albumin, 25-OH vitamin D; if systemic diseases are suspected - ANA, anti-centromere/anti-Scl-70, muscle enzymes (CPK/LDH) and inflammatory markers. In gout - uric acid; if in doubt - puncture of a node/joint with polarizing microscopy (urate crystals). [37]

Step 3: Verification of complex forms. If calciphylaxis is suspected, a skin biopsy should be performed with caution (risk of worsening the wound): medial calcification and arteriolar thrombosis are identified; Tc-99m scintigraphy may be helpful (accumulation in foci). In tumoral calcinosis, hyperphosphatemia should be confirmed and FGF23/GALNT3/KL genetic testing performed. [38]

Step 4 - Etiologic audit. Analysis of medications (warfarin, calcium/vitamin D), dialysis parameters (dialysate calcium, adequacy, phosphate binders), metabolic causes of hyper/hypophosphatemia. In case of cutaneous osteoma, histology confirms mature bone tissue in the dermis. [39]

Table 5. Diagnostic minimum

Block	What to do	For what
Laboratory	Ca, P, Ca×P, Mg, PTH, creatinine, albumin, 25-OH-D	Distinguish between metastatic/dystrophic mechanism
Immunology	ANA, anti-centromere, anti-Scl-70, CPK	Search for SKL/DM
Image	X-ray/ultrasound; in cases of mass CT/MRI	Confirm calcifications, assess volume
Biopsy	Selective (calciphylaxis/unclear cases)	Morphology (arterioles vs dermis)
Specifics	Urates; FGF23 pathway genetics	Tophi; tumoral calcinosis [40]

Differential diagnosis

• Pilomatrixoma (benign hair matrix tumor): a dense calcific nodule in children/young adults, with an "eggshell" appearance on x-ray - often confused with focal calcification.
• Xanthomas/reticulohistiocytosis - yellowish nodules without calcium; dermatoscopy/histology is helpful.
• Gouty tophi are whitish nodules with a chalky appearance and positive urate crystals under a polarizing microscope; they require systemic urate reduction.
• Cutaneous osteoma - true bone in the dermis (osteocytes/osteons), not calcium salts; management is different. [41]

Table 6. Differential features

State	Pain	X-ray/ultrasound	Laboratory	Histology
Calcification	±	Calcifications	Ca/P - by type	Calcium in the dermis
Calciphylaxis	Strong	Vascular calcification	Frequently ↑P, CKD	Kaltsif. arterioles
Tophi	±	Tight knots	↑Uric acid	Urates in bulk
Osteoma	−/±	Bone inclusions	Norm	Mature bone [42]

Treatment

The basic principle: treat the cause and control symptoms. In dystrophic calcinosis, the focus is on controlling the underlying disease (SCL/DM), protecting the skin, preventing injury and infection, and locally treating ulcers. Pain management is important: stepwise regimens are used; in calciphylaxis, opioids and multidisciplinary analgesia are often required. [43]

Systemic anti-inflammatory and disease-modifying therapy in KLS/DM indirectly reduces calcinosis (by controlling inflammation). According to reviews in rheumatology, immunobiological options (rituximab, TNF-α inhibitors, abatacept) are discussed in refractory cases, but the data are primarily observational; in juvenile dermatomyositis, some recommendations allow infliximab/abatacept/intravenous immunoglobulins to control the active process and associated calcinosis. [44]

Calcium antagonists (most commonly diltiazem) are a traditional treatment option for calcinosis cutis; results are mixed: in some series, partial alleviation and reduction of pain, while in others, minimal effect. They are chosen as a low-risk treatment option, especially for small symptomatic lesions. [45]

Bisphosphonates (oral/intravenous) - reduce bone resorption and macrophage activity; there is no class A evidence for calcinosis cutis, but case reports and small series with improvement have been reported (including in juvenile dermatomyositis). The decision is individual, especially in cases of multiple painful lesions. [46]

Sodium thiosulfate (STS) is a key off-label agent. Topical, intralesional, and systemic regimens are used for calcinosis cutis; retrospective series have noted palliation, pain reduction, and ulceration, but responses are variable. For calciphylaxis, intravenous STS is part of standard multi-therapy. Newer formulations (eg, topical metabisulfite) are being experimented with. [47]

Minimally invasive techniques include extracorporeal shock wave therapy (ESWT/ESWL), fractional lasers, and ultrasound-guided mechanical ablation of calcifications. Shock wave therapy can reduce pain and sometimes the volume of calcifications; the evidence base is limited to case reports and small studies. Lasers are used locally for small, superficial deposits. [48]

Surgical excision is the best treatment for localized symptomatic lesions, especially if they become ulcerated/infected and interfere with function. The key is to completely remove the lesions and allow them to heal; however, with tumoral calcinosis, recurrence is high without correction of hyperphosphatemia. In cutaneous osteoma, excision solves the cosmetic problem. [49]

Gouty tophi require systemic urate-lowering therapy with a treat-to-target strategy: allopurinol is the first-line drug; in case of insufficient response, febuxostat, uricosurics, or a combination. In refractory tophaceous gout, pegloticase (often in combination with methotrexate to enhance the sustainability of the response) is used. Local interventions without urate control are ineffective. [50]

Calciphylaxis is treated multimodally: intensification of dialysis and correction of dialysate calcium, strict phosphate control (diet, phosphate binders without calcium), discontinuation of warfarin, administration of intravenous sodium thiosulfate, aggressive wound care and antibiotic therapy for infection; in persistent secondary hyperparathyroidism - cinnacalcet or parathyroidectomy. A new option for phosphate control in dialysis patients is tenapanor (an NHE3 inhibitor), approved as an add-on therapy, which can help reduce P and Ca×P product. [51]

In hyperphosphatemic tumor calcinosis, the foundation is phosphate reduction: a low-phosphate diet, non-calcium phosphate binders, acetazolamide/probenecid (as indicated), and adjuvant STS; surgery is reserved for patients with metabolic stabilization. Research into targeted approaches to the FGF23 axis is ongoing; clinical practice is currently limited to case reports. [52]

Table 7. Therapeutic options in brief

Situation	First line	Additional/new
Dystrophic calcinosis	Control of the underlying disease, wound care	Diltiazem, bisphosphonates, STS (local/syst), ESWT/laser, surgery
Calciphylaxis	Dialysis optimization, calcium-free phosphate binder, IV STS, wound care, antibiotics	Cinnacalcet/PTE, tenapanor as antiphosphate support
Tumorous calcinosis	Low-P, non-Ca-binding diet	Acetazolamide/probenecid, STS; surgery after stabilization
Tophi (gout)	Allopurinol, target <360 μmol/L (<6 mg/dL)	Febuxostat/uricosurics; refractory - pegloticase + MTX [53]

Prevention

In patients with autoimmune diseases of the skin and connective tissue, prevention of calcinosis includes early and adequate control of inflammation, gentle skin care, prevention of injuries and secondary infections, and education on wound/ulcer care. [54]

For dialysis patients - strict phosphate control, avoidance of calcium-containing binders if Ca×P is high, optimization of the dialysis prescription, caution with vitamin D and PTH monitoring; avoid warfarin if alternatives are available. [55]

For gout, treat-to-target urate-lowering therapy with lifestyle modification prevents the growth of tophi and their skin complications. [56]

Forecast

The prognosis for dystrophic calcinosis depends on control of the underlying disease and the size/location of the lesions; localized, non-ulcerative lesions can often be controlled with minimally invasive procedures. In tumoral calcinosis, recurrence after removal is common without correction of hyperphosphatemia. [57]

Calciphylaxis remains life-threatening: even with modern multi-therapy, the 1-year mortality in cohorts is high; the key to improvement is early diagnosis, aggressive phosphate control and a multidisciplinary approach. [58]

In gout, systemic urate-lowering therapy can lead to regression of tophi, reducing the need for local interventions; once target uric acid levels are achieved, the prognosis for the skin is favorable. [59]

FAQ

Is it "calcium salts" or "bone"?
Both occur. In calcification, it's calcium salts; in cutaneous osteoma, it's mature bone tissue in the dermis. Treatment strategies vary. [60]

Is a biopsy always necessary?
No. In typical superficial calcifications and a clear systemic cause, clinical and instrumental confirmation is sufficient. A biopsy is mandatory if there is doubt or a tumor has been ruled out; in calciphylaxis, it is useful, but the risk-benefit is assessed individually. [61]

Is there a "cure-all" for tophi?
There's no one-size-fits-all approach. There are multi-component strategies, ranging from diltiazem/bisphosphonates and sodium thiosulfate to ESWT/lasers/surgery; the choice depends on the type and severity. For gout, systemic urate-lowering therapy is the solution to the tophi problem. [62]

What's new in 2023-2025?
In nephrology, the use of tenapanor for phosphate control in dialysis patients has become established; in dermatology, the search for optimal sodium thiosulfate regimens (including topical forms) and local energy-based technologies continues. For juvenile dermatomyositis, the role of biological therapy in refractory calcinosis is being discussed. [63]

Summary Table 8. Red Flags and Quick Actions

Situation	What's alarming	Immediate steps
Suspected calciphylaxis	Severe pain, livedo/necrosis, CKD/dialysis	Urgent nephrologist/dermatologist: initiate P monitoring (including consideration of tenapanor), discontinue warfarin, IV sodium thiosulfate, wound care
Tophi	Nodes + arthritis, urate crystals	Rheumatologist: urate-lowering to target levels, prevention of attacks
Tumorous calcinosis	Large periarticular masses, ↑P	Endocrinologist/nephrologist: phosphate reduction, genetic counseling
Skin osteoma	Hard "bone" papule	Dermatologist/surgeon: excision when indicated