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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 2  |  Page : 556-560
Nonuremic calciphylaxis in a patient with multiple myeloma and rheumatoid arthritis

Department of Nephrology, Mohamed VI Medical Center, Marrakesh, Morocco

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Date of Submission06-Mar-2019
Date of Decision30-Apr-2019
Date of Acceptance02-May-2019
Date of Web Publication09-May-2020


Calciphylaxis is a rare and highly morbid condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. Calciphylaxis predominantly affects patients with chronic kidney disease treated by dialysis but is also described in patients with normal kidney function. We report a rare case of a patient who presented with calciphylaxis associated with multiple myeloma and rheumatoid arthritis. With a better understanding of its pathophysiology, more effective therapies are being developed.

How to cite this article:
Bouchemla N, Laamani A, Chettati M, Fadili W, Laouad I. Nonuremic calciphylaxis in a patient with multiple myeloma and rheumatoid arthritis. Saudi J Kidney Dis Transpl 2020;31:556-60

How to cite this URL:
Bouchemla N, Laamani A, Chettati M, Fadili W, Laouad I. Nonuremic calciphylaxis in a patient with multiple myeloma and rheumatoid arthritis. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 Jun 17];31:556-60. Available from: https://www.sjkdt.org/text.asp?2020/31/2/556/284038

   Introduction Top

Calciphylaxis has been defined as a tissue sensitivity to calcification affecting small and medium-sized vessels, especially of the skin, and causing necrosis.[1] It presents with painful indurated violaceous skin lesions that ulcerate, often with an overlying jagged black eschar.[2] This rare phenomenon has been reported pre-dominantly in obese women, and in association with chronic kidney disease, dialysis (in 90% of the cases), renal transplantation, parathyroid dysfunction, primary hyperpara- thyroidism, lymphoma, leukemia, and multiple myeloma. [3] We report here a rare case of association of calciphylaxis with rheumatoid arthritis, amyloidosis, and multiple myeloma.

   Case Report Top

A 62-year-old woman was admitted to hospital for edema evolving for two months with oliguria and polyarthralgia. In her medical history, she was on follow-up for rheumatoid arthritis for 20 years. On examination, the patient was conscious with 15/15 Glasgow coma scale with normal heart rate 80 beats/min, blood pressure 110/54 mm Hg, and deformities of the toes and phalanges.

Dermatological examination found large painful sores, which appeared eight months ago at the back of both legs, with a necrotic background, well-defined edges, and violet periphery of livedoid appearance.

Laboratory showed proteinuria of 24 h at 5.87 g, an increased sedimentation rate at 135 mm, serum creatinine at 8 mg/L, urea at 0.23 The hemogram revealed anemia at 9.4 g/dL, WC at 8240 and platelets at 490,000 with a prothrombin time of 59%. Immunoassay showed positive rheumatoid factor and anti-cyclic citrullinated peptide positive. Electrophoresis of serum proteins showed a narrow band of the monoclonal band in the gamma zone. Immunoelectrophoresis has demonstrated monoclonal gammopathy of IgG Lambda type [Figure 1]. X-rays of the hands showed a bilateral carpal synostosis especially on the left hand [Figure 2]. Radiography of the whole spine showed vertebral fractures with diffuse malalignment.
Figure 1: Monoclonal gammapathy of IgG Lambda type.

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Figure 2: Bilateral fused carpite and mediacalcosis.

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Radiological exams showed diffuse interstitial fibrosis with mediastinal widening on chest X-ray, diffuse vascular calcifications in the pelvic X-ray [Figure 3] and bilateral carotid atherosclerotic calcifications predominant in the carotid bulbs [Figure 4], atheromatous infiltration with media calcification of the thoracoabdominal aorta and its branches of bifurcation on thoracoabdominopelvic CT [Figure 5].
Figure 3: Vascular calcifications.

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Figure 4: Bilateral carotid atherosclerotic calcifications.

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Figure 5: Atheromatous infiltration with mediacalcose of the thoracoabdominal aorta and its branches of bifurcation.

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Radiological examinations showed diffuse interstitial infiltrates and fibrosis with mediastinal widening and minimal pleural effusion on chest X- ray, diffuse vascular calcifications with diffuse bone demineralisation with biconcave compression of the body vertebral with respect to the posterior wall. Biopsy of accessory accessory salivary glands showed AL amyloid deposits. The bone marrow examination showed a plasma showed a plasma cell excess of 17.4% with the presence of hemaphagocytes. The patient died during her hospitalization due to septic shock from complications of cutaneous infections.

   Discussion Top

Calciphylaxis is most commonly reported in patients in the 5th decade of life; however, it has also been described in patients significantly younger, including children. Calciphy- laxis is more commonly seen in women compared with men, with a female predominance.[4],[5],[6]

In a systemic review of 36 nonuremic calci- phylaxis cases, primary hyperparathroidism, malignancies, autoimmune disease, diabetes mellitus, and alcoholic liver disease were the most notable associated comorbid conditions.[7] In addition, case reports have also described nonuremic calciphylaxis as a complication of Hodgkin lymphoma, teriparatide therapy, gastric bypass surgery, and hypoparathyroi- dism.[8],[9],[10],[11] Several autoimmune conditions have also been reported in association with calci- phylaxis such as systemic lupus erythema- tosus, antiphospholipid antibody syndrome, temporal arteritis, and rheumatoid arthritis.

The one-year mortality in patients with calci- phylaxis is reported at 45%-80%, with ulcerated lesions associated with higher mortality compared with nonulcerated lesions and sepsis being the leading cause of death.[12],[13]

While the exact pathogenesis of calciphylaxis remains unclear, histopathological finding include small vessel endovascular fibrosis, fibrin thrombi, intimal proliferation, oblite- rative vasculopathy, tissue ischemia calcifi-cation, panniculitis, and subcutaneous fat necrosis.[7],[14],[15]

Although etiopathogenesis remains unclear, some studies have postulated the role of inhibitors of vascular calcification (fetuin-A and matrix Gla protein). Therefore, various stimuli, for example, a chronic inflammatory substrate as in our case, might reduce the activity of these factors leading to vascular calcification.[16],[17]

The true syndrome of calciphylaxis is characterized by its development in three phases: (1) sensitization produced by calcium mobilizing agents, such as Vitamin D and parathyroid hormone, or interventions like bilateral nephrectomy; (2) the critical period of latency between sensitization and the induction of calciphylaxis; and (3) the action of induction agents which, when applied locally, produce a response in the skin or connective tissue (local calciphylaxis) but, if administered parente- rally, trigger responses in different organs.[18]

Clinically, it begins as a painful rash that progresses to retiform purpura and then to purplish plaques that tend to skin necrosis and ulceration. They usually affect the lower limbs, particularly the proximal half and lower abdomen. These injuries are very painful, symmetrical and do not affect distal pulses.[3]

Histology is the main diagnostic tool to see calcification of the vascular wall, with intimal hyperplasia, thrombosis in small surrounding vessels and occasional signs of panniculitis and dermoepidermal necrosis as a result of ischemia. The vessels of the hypodermis are particularly involved, hence the importance of performing a deep skin biopsy. Sometimes calcium deposits can be subtle. Thus, it is important to perform serial sectioning and even specific staining for calcium in order to detect small granular deposits that otherwise might remain unnoticed.[19]

Prognosis of calciphylaxis is generally poor and is considered a devastating and life- threatening condition. Patients often die, most commonly from sepsis, with the bacterial port of entry being skin ulcerations.[20]

Cinacalcet and parathyroidectomy have been proposed as therapeutic options in cases involving primary or secondary hyperparathyroi- dism. Intravenous, topical or intra-lesional sodium thiosulfate has also been proven useful, known for its action as an antidote for cyanide poisoning or tumoral calcinosis. Its effect would be to increase the solubility of calcium phosphate by forming highly soluble complex of calcium thiosulfate. Other proposed treatments are biphosphonates or hyperbaric oxygen therapy.[3]

   Conclusion Top

Although calciphylaxis is more frequent in patients with renal failure undergoing dialysis and/or disorders of calcium and phosphorus metabolism, the report of this disease in our patient with rheumatoid arthritis and multiple myeloma, alerts us to the need to be aware of these entities as well.

Conflict of interest: None declared.

   References Top

Ozbalkan Z, Calguneri M, Onat AM, Ozturk MA. Development of calciphylaxis after long- term steroid and methotroxate use in a patient with rheumatoid arthritis. Intern Med 2005; 44:1178-81  Back to cited text no. 1
Halasz CL, Munger DP, Frimmer H, Dicorato M, Wainwright S. Calciphylaxis: Comparison of radiologic imaging and histopathology. J Am Acad Dermatol 2017;77:241-6  Back to cited text no. 2
Lloret R, Moles P, Barrado S, Gimeno C. Calcifilaxia no uremica en unapaciente con arthritis reumatoide. Med Clin (Barc) 2016; 146:44-5  Back to cited text no. 3
Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR. Calciphylaxis: Natural history, risk factor analysis, and outcome. J Am Acad Dermatol 2007;56:569-79  Back to cited text no. 4
Nigwekar SU, Bhan I, Turchin A, et al. Statin use and calcific uremic arteriolopathy: A matched case-control study. Am J Nephrol 2013;37:325-32  Back to cited text no. 5
Ahmed S, O’Neill KD, Hood AF, Evan AP, Moe SM. Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis 2001;37:1267-76  Back to cited text no. 6
Nigwekar SU, Wolf M, Sterns RH, Hix JK. Calciphylaxis from nonuremic causes: A systematic review. Clin J Am Soc Nephrol 2008;3:1139-43  Back to cited text no. 7
Allegretti AS, Nazarian RM, Goverman J, Nigwekar SU. Calciphylaxis: A rare but fatal delayed complication of Roux-en-Y gastric bypass surgery. Am J Kidney Dis 2014;64: 274-7  Back to cited text no. 8
Spanakis EK, Sellmeyer DE. Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1-34)] therapy in the setting of chronic warfarin and glucocorticoid treatment. Osteoporos Int 2014;25:1411-4  Back to cited text no. 9
Sibai H, Ishak RS, Halawi R, et al. Non- uremic calcific arteriopathy in relapsed/refractory Hodgkin’s lymphoma: A previously unreported association. J Clin Oncol 2012;30: e88-90  Back to cited text no. 10
Erdel BL, Juneja R, Evans-Molina C. A case of calciphylaxis in a patient with hypopara- thyroidism and normal renal function. Endocr Pract 2014;20:e102-5  Back to cited text no. 11
Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: Risk factors, outcome and therapy. Kidney Int 2002;61:2210-7  Back to cited text no. 12
Hafner J, Keusch G, Wahl C, et al. Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphy- laxis): A complication of chronic renal failure and benefit from parathyroidectomy. J Am Acad Dermatol 1995;33:954-62  Back to cited text no. 13
Rogers NM, Coates PT. Calcific uraemic arteriolopathy: An update. Curr Opin Nephrol Hypertens 2008;17:629-34  Back to cited text no. 14
Rogers NM, Teubner DJ, Coates PT. Calcific uremic arteriolopathy: Advances in patho- genesis and treatment. Semin Dial 2007;20: 150-7  Back to cited text no. 15
Sowers KM, Hayden MR. Calcific uremic arteriolopathy: Pathophysiology, reactive oxygen species and therapeutic approaches. Oxid Med Cell Longev 2010;3:109-21  Back to cited text no. 16
Malabu UH, Roberts LJ, Sangia KS. Calciphylaxis in a morbidly obese woman with rheumatoid arthritis presenting with severe weight loss and Vitamine D deficiency. Endocr Pract 2011 ;17:e104-8  Back to cited text no. 17
Magro CM, Simman R, Jackson S. Calciphylaxis: A review. J Am Col Certif Wound Spec 2010;2:66-72  Back to cited text no. 18
Mochel MC, Arakaki RY, Wang G, Kroshinsky D, Hoang MP. Cutaneous calciphylaxis: A retrospective histopathologic evaluation. Am J Dermatopathol 2013;35:582- 6  Back to cited text no. 19
Dauden E, Onate MJ. Calciphylaxis. Dermatol Clin 2008;26:557-68, ix.  Back to cited text no. 20

Correspondence Address:
Nadia Bouchemla
Department of Nephrology, Mohamed VI Medical Center, Marrakesh
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DOI: 10.4103/1319-2442.284038

PMID: 32394936

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