Unusual Cause of Iatrogenic Calcifications : JCR: Journal of Clinical Rheumatology

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Unusual Cause of Iatrogenic Calcifications

Thoma, Anna MD

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JCR: Journal of Clinical Rheumatology 29(2):p e6-e9, March 2023. | DOI: 10.1097/RHU.0000000000001918
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A 65-year-old woman presented with painful skin indurations and soft tissue atrophy of proximal upper (Fig. 1) and lower extremities. These areas corresponded to those in which the patient had received subcutaneous pethidine injections due to chronic knee pain of 5 years in duration. Blood tests were normal except for positive antinuclear antibody test (ANAs 1:320). Radiographs demonstrated circumscribed calcifications in the soft tissue of upper and lower extremities (Figs. 2 and 3). The patient was diagnosed with iatrogenic calcifications after repeated subcutaneous pethidine injections.

Patient’s left arm with atrophy of the skin and subcutaneous tissue.
X-ray of the right upper arm with subcutaneous calcifications.
X-ray of the pelvis with extended calcifications in the soft tissue of the legs. Hip prosthesis on the left side.


To our knowledge, this is the first description of calcinosis cutis after repetitive local pethidine injections. The prescription of pethidine (also known as meperidine) is strictly regulated in Switzerland, and pethidine injections are not a common practice for the treatment of chronic pain conditions. However, misuse in general practice can occur. We did not think her (+) ANAs were attributable to autoimmune disease because she had no clinical signs; all other blood tests were normal including the blood cell count, C-reactive protein and blood sedimentation rate, creatinine, creatinine kinase, thyroid function tests, and the urine sediment. The specific autoimmune antibodies, especially anti–double-stranded DNA, anti-Ro/La, and anti–Scl-70, were also all negative. We have interpreted the positive ANA titer in our patient (1:320) was due to the extended tissue damage.1,2 Iatrogenic calcifications have been described after local injections of other substances.3–7 Other forms of calcinosis cutis are dystrophic, metastatic, idiopathic calcifications, and calciphylaxis and differ by their pathogenesis and associated disorders.

Four differential diagnoses:

  • (1) Local trauma with subsequent dystrophic calcification
  • (2) Connective tissue diseases, for example, systemic sclerosis and lupus erythematodes
  • (3) Infectious panniculitis
  • (4) Hyperparathyroidism


1. Herrera-van Ootsdam DA, Esparza-Ibarra E, Ramirez-Sandoval R, et al. Apoptosis and necrosis increase antigenicity of proteins recognized by antinuclear antibodies. Reumatismo. 2004;53:156–161.
2. Du L, Fukushima S, Sallmyr A, et al. Exposure of HEP-2 cells to stress conditions influences antinuclear antibody reactivity. Clin Diagn Lab Immunol. 2002;9:287–294.
3. Meissner M, Varwig D, Beier C, et al. Dystrophic calcinosis cutis after subcutaneous administration of para-aminosalicylic acid for treatment of pulmonary tuberculosis. J Dtsch Dermatol Ges. 2006;4:489–491.
4. Walsh JS, Fairley JA. Calcifying disorders of the skin. J Am Acad Dermatol. 1995;33:693–706.
5. Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis: part l. Diagnostic pathway. J Am Acad Dermatol. 2011;65:1–12; quiz 13–14.
6. Hoelen DW, Tjan DH, van Vugt R, et al. Severe local vancomycin induced skin necrosis. Br J Clin Pharmacol. 2007;64:553–554.
7. Zenati N, Khouri C, Schwebel C, et al. Skin necrosis and calcifications after extravasation of vancomycin: a localised form of calciphylaxis?J Wound Care. 2021;30:390–393.

calcinosis cutis; dystrophic calcification; local injections; iatrogenic calcification; pethidine

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