P28 Recalcitrant exuberant digital calcinosis cutis in a patient of CREST syndrome - A case report

Abstract Introduction/Background Calcinosis cutis is dystrophic soft-tissue calcification associated with connective tissues diseases, especially scleroderma, systemic lupus erythematosus or dermatomyositis. It occurs in all subsets of scleroderma but is more prominent in patients with limited scleroderma (CREST syndrome) and in those with anticentromere antibody. Dystrophic calcinosis can be associated with severe pain, decreased mobility, increased risk of infection, and significantly decreased quality of life. We report our experience with a case of refractory calcinosis cutis in a patient with multiple comorbidities. Description/Method We are presenting a 62-year-old lady diagnosed with Limited Cutaneous Sclerosis (CREST syndrome) with background of Giant Cell Arteritis, Osteoporosis, TIA and Hypothyroidism. Patient has had a history of onset of Raynaud’s at the age of 20 years. Around the age of 50, she started developing gastrointestinal features and subcutaneous nodules on her fingers. The painful nodules on her fingers were her predominant symptom. These nodules appeared as multiple hardened exuberant erythematous-whitish nodules, some having a chalky appearance, around her fingers. A clinical diagnosis of calcinosis cutis was made. Other features included sclerotic cutaneous findings on her face and fingers (sclerodactyly), prominent facial telangiectasia and esophageal reflux. In light of suspected CREST syndrome, patient was extensively investigated, and diagnosis was confirmed. Antinuclear and anti-centromere (anti-Th and anti-RNP) antibodies were positive. X-ray showed extensive calcinosis in the soft tissue of the fingers. Serum calcium and phosphorus levels were within the normal ranges. Pulmonary function test was normal. For her ongoing digital calcinosis cutis associated with severe pain and recurrent ulceration which was adversely impacting the quality of her life, she was started on low dose aspirin to alleviate her symptoms. This initially helped improve her symptoms, however later stopped responding. Then a trial of low dose Irbesartan at dose of 75 mg was given with which she found no relief. She was referred to higher center and a trail of Minocycline at dose of 50-100mg was given for over 3 months which proved to be of no benefit. Reports suggest bisphosphonates are helpful in Calcinosis cutis and though patient was Zoledronic acid for osteoporosis, her calcinosis cutis continued to grow and ulcerate. In view of recalcitrant nature of these lesions, patient has been referred to the plastic surgeons for surgical modality of treatment currently. Discussion/Results Calcinosis cutis is a rare and chronic condition characterized by deposition of insoluble calcium salts in the skin and subcutaneous tissues. Dystrophic calcinosis is the most common type of calcinosis cutis and is seen in association with autoimmune connective tissue diseases. It is thought to occur as a result of chronic local tissue injury and is a common complication of systemic sclerosis especially the limited form (CREST syndrome: calcinosis, raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia), affecting approximately 25% of these patients. Calcinosis may develop at any time during the disease course and may predate the diagnosis of scleroderma, but typically occurs at least 10 years following diagnosis. Lesions occur on the hands and feet, with a high predilection for fingertips and areas of microtrauma. Raynaud’s and digital ulcers are risk factors for calcinosis in scleroderma, suggesting a role for vascular ischemia. These lesions might be associated with pain, soft tissue swelling, ulcers with toothpaste-like material discharging or deformities, which may lead to functional problems. Treatment of calcinosis cutis is tough and challenging as there is no gold standard treatment. Medical therapy for cutaneous calcinosis is limited and has variable benefits. Multiple treatment approaches with diltiazem, disodium etidronate, probenecid, colchicine, minocycline, low-dose warfarin, intralesional adrenal steroids, abatacept, rituximab, thalidomide have been explored, but no standard treatment has convincingly prevented or reduced calcinosis. Surgery is generally reserved for discrete lesions with problems of recurrent infection, severe pain, or functional impact Despite concerns about recurrence of lesion due to mechanical trauma at the operative site, surgical resection has been effective in treating calcinosis. Treatment with extracorporeal shock wave lithotripsy and carbon dioxide laser therapy have shown promise in a few cases and need further study. Key learning points/Conclusion Pharmacological treatment of calcinosis cutis is difficult and a variety of drugs including bisphosphonates, intralesional corticosteroids, aluminium hydroxide, warfarin and diltiazem, have been tried with limited success. The local excision of painful or ulcerated nodule is the current existing therapeutic potion but local recurrence is common. The present case is of interest because it has features of Raynaud’s phenomenon, heart burn, telangiectasia and sclerodactyly with microscopic finding of calcinosis cutis (CREST syndrome). Patient with crest syndrome often have better prognosis than diffuse systemic sclerosis. Pathologist should be aware about various clinico-pathological categories associated with localized calcium deposition in dermis.

leroderma Overlap conditions are well ently than their limited or diffuse counterients is usually tailored around the organ rity. We present a challenging case of with refractory Raynaud's phenomenon s due to severe autonomic dysfunction.
ld Caucasian lady, non-smoker, who eyes, dry mouth and severe Raynaud's ulceration which became infected 1:400 with Extractable nuclear antigen NA was negative and C4 was low. cryoglobulins are negative. She failed phosphodiesterase 5 inhibitors and (IV) Iloprost which was tried on multiple tried as well. This treatment was complihypotension and multiple fall epi-This was attributed to autonomic Sjogren syndrome. She was initiated on her hypotensive episodes continous immunoglobulins 20gm (over months for autonomic dysfunction with developed recurrent diarrhoea and h was attributed to small bowel overon a gastric emptying scan. She had a was unblocked using Endoscopic Over the next 8 years, she Raynaud's, having failed IV digital sympathectomy. Her postural on multiple occasions necessitating some benefit. In 2020, she was slowly progressing left upper lobe lung o assisted thoracoscopy surgery with was suggestive of adenocarcinoma. In due to an acute/subacute infarct of postural hypotension and requires regto manage her symptoms. She is also phenomenon. a case of overlap of Sjogren syndrome nt of Refractory Raynaud's as was challenging. This case gave us the treatment options available for with poor outcome. She also struggled to postural hypotension and gascan be seen in upto 50% of patients with failure is often thought to be immune This makes way for the use of intraveeresis to treat these conditions as ed risk of lung carcinoma with scleroc dysfunction can also present as lung carcinoma, however it is more oma and our patient was diagnosed have to wait and see if the resection effect on her dysautonomia. Overlap connective tissue diseases view of extensive disease heterogeneity.
of challenges in managing Difficult Treating physicians need to be and regular close monitoring conference gives us the opportunity to oaches for her.

Croydon, United Kingdom
Introduction/Background: Systemic sclerosis is a chronic, progressive, multisystemic autoimmune disease in which there is excessive collagen deposition in the dermis and internal organs. It is commonly categorized into limited cutaneous or diffuse cutaneous systemic sclerosis. In more than 80% of patients there is GI involvement. Gut complications can impair oral intake, absorption and even faecal continence, and consequently can have severe adverse effect on quality of life. With disease progression, management of GI symptoms may become more of a challenge. We present a challenging case of SSs with esophageal involvement along with severe regurgitation who eventually responded to a specific prokinetic. Description/Method: 70 y/o female initially presented to gastroenterology clinic in 2013 due to dysphagia to solids and was found to have benign fibrotic oesophageal stricture for which she had therapeutic dilatation, (normal biopsy result). Subsequently, she had barium swallow which showed severe regurgitation. Manometry confirmed severely hypo-contractile oesophagus thus she was referred to rheumatology for suspected connective tissue disorder. On initial review, she did not describe typical inflammatory symptoms, scleroderma, sclerodactyly, Raynaud's phenomenon, digital ulcers, calcinosis, telangiectasia or any other connective tissue features but was diagnosed with limited cutaneous systemic sclerosis due to ANA & anticentromere antibody positivity, severe oesophageal dysmotility and diagnosis of mild pulmonary hypertension (on right heart catheter studies). Her main disabling SSs symptom was refractory belching, intermittent dysphagia and reflux disease resulting in poor oral intake and resultant malnutrition. She had 4-week trial of antibiotics to treat for presumptive small intestine bacterial overgrowth (SIBO) due to persistent belching but had no evident improvement. She had multiple endoscopies which only showed grade B oesophagitis due to which she remained on high dose PPI (Omeprazole 40mg BD) but showed no recurrent stricture. She was also given dual therapy with Ranitidine 150mg bd but derived no benefit. In Rheumatology clinic she was started on erythromycin 250 mg BD as a pro-kinetic and in liquid form for better tolerability (due to the dysphagia) with gradual but significant improvement of her upper GI symptoms. Switching liquid form to tablets/capsule form via GP resulted in worsening symptoms so was switched back to liquid form. GI symptoms worsened again in 2017 and impression was tachyphylaxis to erythromycin. She was started on trial of another pro-kinetic (metoclopramide) but symptoms continued worsening. In view of this she was started back on liquid erythromycin and her symptoms gradually improved again and has remained stable since. Discussion/Results: Systemic sclerosis (SSc) is an incurable connective tissue disorder. It is estimated that approximately 90% of patients with SSc have some form of oesophageal involvement. For first three years, this patient's main symptoms were her upper GI tract issues with reflux and oesophageal dysmotility causing delayed gastric emptying.
Considering the severity of her GI symptoms, it was of great importance for her to maintain a regular follow up with gastroenterology team for a regular review of symptoms and repeat investigations as needed such as multiple repeat UGI endoscopy to ensure no recurrence of oesophageal stricture, monitoring of GORD, and hydrogen breath testing. We recommend for patients with severe oesophageal dysmotility to be started on prokinetics early to control GI symptoms and have minimal impact of these on quality of life. Liquid preparation has shown a significant improvement in symptoms in our patient as compared to tablet or capsule form which actually worsened the symptoms. Key learning points/Conclusion: Dysphagia can be a presenting symptom of systemic sclerosis in some cases. Upper gastro-intestinal symptoms can be severe with significant effect on quality of life. Management of these symptoms can be challenging and may require a combination of treatments. Pro-kinetics mainly erythromycin can have a major positive impact in controlling GI symptoms, Liquid form had better outcome in this case as compared to tablet or capsule form. Poor control of GI symptoms can result in significant malnutrition which is associated with more aggressive disease progression, so GI symptoms management plays a key role in disease control.
scleroderma, systemic lupus erythematosus or dermatomyositis. It occurs in all subsets of scleroderma but is more prominent in patients with limited scleroderma (CREST syndrome) and in those with anticentromere antibody. Dystrophic calcinosis can be associated with severe pain, decreased mobility, increased risk of infection, and significantly decreased quality of life. We report our experience with a case of refractory calcinosis cutis in a patient with multiple comorbidities. Description/Method: We are presenting a 62-year-old lady diagnosed with Limited Cutaneous Sclerosis (CREST syndrome) with background of Giant Cell Arteritis, Osteoporosis, TIA and Hypothyroidism. Patient has had a history of onset of Raynaud's at the age of 20 years. Around the age of 50, she started developing gastrointestinal features and subcutaneous nodules on her fingers. The painful nodules on her fingers were her predominant symptom. These nodules appeared as multiple hardened exuberant erythematous-whitish nodules, some having a chalky appearance, around her fingers. A clinical diagnosis of calcinosis cutis was made. Other features included sclerotic cutaneous findings on her face and fingers (sclerodactyly), prominent facial telangiectasia and esophageal reflux. In light of suspected CREST syndrome, patient was extensively investigated, and diagnosis was confirmed. Antinuclear and anti-centromere (anti-Th and anti-RNP) antibodies were positive. X-ray showed extensive calcinosis in the soft tissue of the fingers. Serum calcium and phosphorus levels were within the normal ranges. Pulmonary function test was normal. For her ongoing digital calcinosis cutis associated with severe pain and recurrent ulceration which was adversely impacting the quality of her life, she was started on low dose aspirin to alleviate her symptoms. This initially helped improve her symptoms, however later stopped responding. Then a trial of low dose Irbesartan at dose of 75 mg was given with which she found no relief. She was referred to higher center and a trail of Minocycline at dose of 50-100mg was given for over 3 months which proved to be of no benefit. Reports suggest bisphosphonates are helpful in Calcinosis cutis and though patient was Zoledronic acid for osteoporosis, her calcinosis cutis continued to grow and ulcerate. In view of recalcitrant nature of these lesions, patient has been referred to the plastic surgeons for surgical modality of treatment currently. Discussion/Results: Calcinosis cutis is a rare and chronic condition characterized by deposition of insoluble calcium salts in the skin and subcutaneous tissues. Dystrophic calcinosis is the most common type of calcinosis cutis and is seen in association with autoimmune connective tissue diseases. It is thought to occur as a result of chronic local tissue injury and is a common complication of systemic sclerosis especially the limited form (CREST syndrome: calcinosis, raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia), affecting approximately 25% of these patients. Calcinosis may develop at any time during the disease course and may predate the diagnosis of scleroderma, but typically occurs at least 10 years following diagnosis. Lesions occur on the hands and feet, with a high predilection for fingertips and areas of microtrauma. Raynaud's and digital ulcers are risk factors for calcinosis in scleroderma, suggesting a role for vascular ischemia. These lesions might be associated with pain, soft tissue swelling, ulcers with toothpaste-like material discharging or deformities, which may lead to functional problems. Treatment of calcinosis cutis is tough and challenging as there is no gold standard treatment. Medical therapy for cutaneous calcinosis is limited and has variable benefits. Multiple treatment approaches with diltiazem, disodium etidronate, probenecid, colchicine, minocycline, low-dose warfarin, intralesional adrenal steroids, abatacept, rituximab, thalidomide have been explored, but no standard treatment has convincingly prevented or reduced calcinosis. Surgery is generally reserved for discrete lesions with problems of recurrent infection, severe pain, or functional impact Despite concerns about recurrence of lesion due to mechanical trauma at the operative site, surgical resection has been effective in treating calcinosis. Treatment with extracorporeal shock wave lithotripsy and carbon dioxide laser therapy have shown promise in a few cases and need further study. Key learning points/Conclusion: Pharmacological treatment of calcinosis cutis is difficult and a variety of drugs including bisphosphonates, intralesional corticosteroids, aluminium hydroxide, warfarin and diltiazem, have been tried with limited success. The local excision of painful or ulcerated nodule is the current existing therapeutic potion but local recurrence is common. The present case is of interest because it has features of Raynaud's phenomenon, heart burn, telangiectasia and sclerodactyly with microscopic finding of calcinosis cutis (CREST syndrome). Patient with crest syndrome often have better prognosis than diffuse systemic sclerosis. Pathologist should be aware about various clinico-pathological categories associated with localized calcium deposition in dermis.