Calcinosis Cutis and Negative Pressure Wound Therapy as Adjuncts to Surgical Management: Case Report and Review of the Literature

Calcinosis cutis (CC), or calcium deposition in soft tissue, can cause significant morbidity associated with arthralgias and ulceration. This condition has an elusive pathophysiology and is often associated with autoimmune disorders, significantly impacting the disease burden. The clinical presentation of CC varies, and there is no gold standard treatment modality. The case of a 50-year-old woman with scleroderma and a rare presentation of milky drainage of a left hip ulcer secondary to underlying CC that was treated successfully with surgery and negative pressure wound therapy is reported herein. Also included is a review of the literature of the medical and surgical modalities used in the management of this debilitating condition.

Calcinosis cutis (CC), or calcium deposition in soft tissue, can cause significant morbidity associated with pain, especially near joints and areas of ulceration. The specific incidence and prevalence of the disease in the general population is unknown, but it is associated with many different autoimmune connective tissue diseases (ACTDs). It is seen in 25% of all patients with systemic sclerosis, especially those with calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome; in 11% to 20% with classic dermatomyositis; and in 44% to 70% of those with juvenile dermatomyositis.¹ It is generally understood that similar to the associated ACTDs, CC is more common in women than in men. 

A 50-year-old woman with a 2-year history of scleroderma, bilateral hip nodules, and diabetes mellitus presented to the emergency room at Flushing Hospital Medical Center (Queens, NY) with a chief complaint of a draining wound over her left posterior hip in March 2014 (Figure 1). The nodules had been present for about 2 years; however, they only drained 3 days prior to presentation. She denied previous hospitalization and recent antibiotic use. Her surgical history was significant for a cholecystectomy, but the rest of her history of the present illness was noncontributory. She was hospitalized for 15 days, and during her stay and on follow-up visits, she was instructed by the clinician as per methods discussed in previously published papers in the literature.^2-6 

Physical examination revealed a left hip acute necrotic wound draining a white chalky fluid with calcinosis and sclerodactyly. Her initial laboratory findings were significant for a white blood cell count of 19.5, anemia, thrombocytosis, neutrophilia with left shift, and lymphocytopenia. Metabolic panel showed mild hyponatremia at 132 mmol/L, erythrocyte sedimentation rate of 120 mm/hour, C-reactive protein of 20.6 mg/L, hyperglycemia at 195 mg/dL, uremia, and decreased CO₂. Her calcium level was within normal limits at 8.2 mg/dL; her parathyroid hormone (PTH), vitamin D, and phosphorus levels were not tested, and no antibody testing was performed.

An x-ray of the left hip showed extensive bilateral soft tissue calcifications with ossification, a chest x-ray showed calcifications overlying the bilateral shoulder regions, and an x-ray of the left shoulder showed chronic calcifications. A computed tomography (CT) scan without contrast of her chest showed fibrotic changes, likely from scleroderma. Due to these findings, the patient was diagnosed with left hip cellulitis with leukocytosis, underlying CC, and she was admitted to the regular medical 4N1 floor, prescribed 1 g of  vancomycin every 12 hours, and underwent surgical debridement. 

She underwent surgical debridement of the necrotic wound of the left hip in the operating room on hospital day 2. The left hip wound drained approximately 200 mL of thick, whitish, chalky fluid with calcinosis fragments (Figure 2). A wound and tissue culture were collected. Necrotic skin edges, subcutaneous tissue, and muscle planes were removed along with fibrinous deposits. The wound opening measured 2 cm x 3 cm but tunneled about 6 cm deep. 

Her leukocyte count trended downwards to 17.2, 11.9, and 6.8 on hospital days 2, 3, and 4, respectively. Wound culture was positive for methicillin-resistant Staphylococcus aureus and vancomycin was changed from every 12 hours to every 8 hours. Negative pressure wound therapy (NPWT; VAC Therapy; KCI, an Acelity Company, San Antonio, TX) was applied at -125 mm Hg for 12 days (Figure 3). The NPWT drainage was chalky and included sediment (Figure 4). She was later discharged 14 days after presentation with resolution of her presenting symptoms with a total of 10 follow-up visits in the wound clinic every 2 to 3 weeks. Upon discharge, the wound was about 2 cm x 2.5 cm x 1 cm, and no further antibiotics were necessary as she had finished her 14-day course of vancomycin. Her wound was healing well at 3 weeks after presentation, with granulation tissue and viable margins (Figure 5).

She presented in August 2016 (5 months after her initial visit) with shortness of breath and dry cough and was found to have a moderate-sized pericardial effusion with an ejection fraction of 20% to 25%, severe left ventricle systolic failure, and moderate pulmonary hypertension attributed to her systemic sclerosis. She was on hydroxychloroquine 200 mg daily for her scleroderma with pulmonary fibrosis at this time. She was referred and transferred to a tertiary cardiac hospital for further workup and management of her interstitial lung disease, heart failure, and pulmonary hypertension. Her wound at that time was about 1 cm x 1.2 cm x 0.9 cm (Figure 6).

Pathophysiology

Various theories have been suggested regarding the elusive pathophysiology of CC.^1,4,7 Local alkaline phosphatase (ALP) elevations may lead to hydrolysis of extracellular pyrophosphates, which usually act to inhibit calcium deposition.⁷ Another theory suggests the phosphate bound to necrotic injured cells as seen in ACTDs serve as a nidus for dystrophic calcification.⁸ Lastly, tissue injury may increase cell membrane permeability to calcium and phosphate, overloading the mitochondria’s ability to sequester the ions, which leads to cytosolic calcium and phosphate crystals.⁹

Calcinosis cutis has been described as dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis subtypes. Of these, dystrophic calcinosis is most common.³ Dystrophic calcinosis is most commonly associated with underlying ACTD-affected tissue and normal calcium/phosphate balance, whereas idiopathic calcinosis is associated with normal calcium/phosphate levels and healthy tissue without underlying ACTD.^1,9 Metastatic calcinosis is due to deposition of calcium salts in healthy tissue with an imbalance in calcium and phosphate. These subtypes can be ruled out in favor of dystrophic calcification via analysis of serum calcium, creatinine, PTH, phosphorus, and vitamin D, among other markers. Skin biopsy and imaging studies are employed as well.

Calcinosis cutis in systemic sclerosis

Patients with diffuse pattern systemic sclerosis present with back pain and concurrent Raynaud’s phenomenon, with additional features of CREST syndrome and pulmonary fibrosis.³ On imaging studies, radiograph and CT may often show large extensive calcifications, which can be scattered in the femoral neck near the thoracic, lumbar spine, and periclavicular region. Physical exam may show limited mobility of segments of the lower extremities; of note, there are no bony erosions as the calcifications are localized in the soft tissues. Serum calcium, phosphate, PTH, and ALP are usually normal. 

Tissue calcinosis may be found with hypercalcemia when there is an underlying illness. In patients with eucalcemic PTH elevation, calcified lesions occur in necrotic or damaged tissue and present as dystrophic calcinosis.^1,9 

The time to diagnosis of CC in underlying systemic lupus erythematosus (SLE) tends to be much longer as the disease is clinically silent in these patients.¹ A study by the Mayo Clinic found that on average, CC occurred more than 20 years after initial diagnosis of SLE.¹ Patients with underlying SLE refractory to medical intervention may present with enlarged CC masses. The initially pea-sized masses may coalesce and produce recurrent ulcers, infections, and abscesses with white, chalky discharge extruding from within the calcified lesions^1,7 (as was the case in the patient reported herein). Lobulated calcified masses can form with central necrosis, which may interfere with movement.

Calcinosis cutis in rheumatoid arthritis (RA)

Though rare, CC patients with underlying RA have been reported.^1,6 Shahi et al⁶ found dystrophic calcinosis of the buttocks and elbow in a patient with RA. Balin et al¹ reported CC involvement in the extremities alone.

Diagnostic modalities

Radiologic studies have consistently shown that plain radiography is able to find CC in all patients with underlying ACTDs.⁵ There are various patterns of calcifications that may present as CC, including nodular, reticular, amorphous, sheet-like, and linear.^1,9 However, the radiologic morphological patterns seen in CC are not always consistent to any specific underlying ACTD.^2,6 

Treatment

Medical intervention has yielded mixed results in its efficacy and its results vary according to studies.^2,7 Calcium channel blockers have been found to have the highest efficacy compared with any other medical intervention.^1,7 Calcium channel blockers promote a decrease in the influx of calcium into the cell, thereby lowering intracellular crystal formation. Colchicine has been reported to have no effect on the calcinosis lesion itself but rather in decreasing secondary inflammation.^2,10 Minocycline also has been shown to be efficacious in treating calcinosis, albeit through an unknown mechanism. It has been postulated² that its positive effects are due to decreasing secondary inflammation, inhibition of collagen lysing enzymes, and calcium chelation. 

Treatment methods that hasten the healing process are associated with decreased morbidity. In light of this, a particularly interesting treatment modality is NPWT. It is used in many different specialties to repair soft tissue defects, assisting in both debridement and removal of soluble inflammatory mediators.⁷ In 2 notable cases of calciphylaxis,^7,8 2 patients were treated with NPWT with varying results. The patient with calciphylaxis who had a low affected total body surface area with early use of NPWT showed significant improvement with contraction and eventual granulation of her chronic wounds. The NPWT use was associated with a significant decrease in wound dressing changes and an accelerated wound closure time postdebridement. Although these cases illustrate the success of NPWT in calciphylaxis treatment, it is reasonable to expect a similar benefit in chronic wound healing and decreased morbidity in other patients with CC with underlying ACTD. The patient presented herein had an unusual presentation of solid and liquid CC, and the application of NPWT helped suction off the drainage, which initially was 300 mL per day, and the drainage decreased gradually.

Treatment involves reducing pain, disability, and morbidity rather than curing it. From a Mayo clinic study,¹ the treatment modalities of the study were categorized based on the severity of the underlying associated ACTD as well as the ACTD itself. The study found that the anatomic distribution of CC varied according to the underlying ACTD type but most commonly was identified on the hands or feet. A calcium channel blocker such as diltiazem along with colchicine was recommended as a first line in addition to surgical excision of symptomatic lesions, physical therapy to improve disability, and wound care to prevent secondary infection of ulcers. Of note, the analgesic effect of extracorporeal shock wave lithotripsy could make surgical excision easier.⁴ While the efficacy of medical approaches other than calcium channel blockers prove to be inconclusive,^1,2,7 surgical excision has been found to be highly efficacious, with improvement of pain, regained function, and decreased recurrence.² 

The manifestations of CC vary based upon the underlying ACTD. Symptoms can be severely debilitating, causing intense pain, decreased range of motion, and chronic or recurrent skin ulcerations that negatively affect the constitutional status. These clinical features may be utilized by physicians to educate patients on expectations for the development of CC over time as the ACTD progresses. Also of importance, ACTD severity does not predict CC severity; the number of treatments do not appear to correlate with ACTD severity, therefore the severity of CC is not affected by treatment length.¹ There is a need for further prospective controlled trials to determine the efficacy of specific drugs on CC depending upon each respective underlying ACTD. This would facilitate individualized treatment options for many patients affected with CC and help improve their quality of life. 

Affiliation: Flushing Hospital Medical Center, Queens, NY

Correspondence: Florian Radu, DO, Flushing Hospital Medical Center, Surgery, 4500 Parsons Boulevard, Queens, NY 11355; fradu@nyit.edu 

Disclosure: The authors disclose no financial or other conflicts of interest.