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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 35  |  Issue : 2  |  Page : 56-58

Cryoglobulinemia presenting as digital gangrene with underlying malignancy


Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala, India

Date of Submission29-Apr-2015
Date of Acceptance08-Jun-2015
Date of Web Publication10-Mar-2016

Correspondence Address:
Mansoor C Abdulla
MD, Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala 679338
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-6530.178460

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  Abstract 

A 55-year-old man presented with multiple joint pains, low-grade fever for 6 months, and blackish discoloration over both feet, which aggravated on exposure to cold, for 2 months. On examination, he was found to have multiple digital gangrene of the lower extremities. On evaluation, he was diagnosed to have multiple myeloma with type 1 cryoglobulinemia. The case is reported to remind the readers to be aware of an underlying plasma cell disease in patients presenting with digital gangrene due to type 1 cryoglobulinemia, which if treated early has good prognosis.

Keywords: Cryoglobulinemia, digital gangrene, multiple myeloma


How to cite this article:
Abdulla MC, Alungal J. Cryoglobulinemia presenting as digital gangrene with underlying malignancy. Egypt J Dermatol Venerol 2015;35:56-8

How to cite this URL:
Abdulla MC, Alungal J. Cryoglobulinemia presenting as digital gangrene with underlying malignancy. Egypt J Dermatol Venerol [serial online] 2015 [cited 2021 Feb 25];35:56-8. Available from: http://www.ejdv.eg.net/text.asp?2015/35/2/56/178460


  Introduction Top


Type 1 cryoglobulinemia is a rare manifestation of plasma cell dyscrasias. It accounts for 10-15% of all cryoglobulinemias and are found in patients with hematological disorders [1] commonly with plasma cell dyscrasias such as multiple myeloma or Waldenstrom macroglobulinemia [2]. The cutaneous manifestations of cryoglobulinemia include palpable purpura, livedo reticularis, ischemic necrosis, and cutaneous ulcerations [1]. Type 1 cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes larger vessels as well [3]. More than 90% of cases of cryoglobulinemia have a known underlying cause; therefore, treatment is focused on the cause of the disorder.


  Case history Top


A 55-year-old man was admitted with multiple joint pains, low-grade fever for 6 months, and blackish discoloration over both feet, which aggravated on exposure to cold, for 2 months. He was taking medications for diabetes for 6 months, and had stopped smoking 20 years ago.

On examination, all his peripheral pulsations were palpable equally and blood pressure was 130/80 mm of Hg. He had multiple black-colored lesions over both the soles and tip of toes [Figure 1]. Systemic examination did not reveal any abnormalities. Investigations showed hemoglobin of 14.7 g/dl, total white blood cell count of 6600/μl, platelet count of 2.6 Χ 10 9 /l, and erythrocyte sedimentation rate of 115 mm in 1 h. Urinalysis showed 1+ albuminuria with 2-4 leukocytes/high power fields. His biochemical parameters revealed the following: random blood sugar (RBS), 151 mg%; urea, 48 mg/dl; creatinine,1.6 mg/dl; sodium, 142 mmol/l; potassium, 4.6 mmol/l; aspartate aminotransferase, 53 IU/l; alanine transaminase, 23 IU/l; alkaline phosphatase, 113 IU/l; total bilirubin, 0.8 mg/dl; direct bilirubin, 0.1 mg/dl; total protein, 9.9 g/dl; albumin, 3.6 g/dl; and globulin, 6.3 g/dl. Peripheral smear was normal. Chest radiograph and ECG were normal. His vasculitis workup, including antinuclear antibody (ANA) profile, rheumatoid factor (RF), c-anti-neutrophil cytoplasmic antibody (cANCA), p-anti-neutrophil cytoplasmic antibody (pANCA), hepatitis B surface antigen (HbsAg), hepatits C virus, human immunodeficiency virus (HIV), and Venereal Disease Research Laboratory (VDRL), were all negative. Cryoglobulins were detected. Serum protein electrophoresis revealed monoclonal gammopathy [Figure 2]. Radiographs of the skull and pelvis showed lytic lesions [Figure 3]. Urinary Bence Jones protein was negative. Bone marrow trephine biopsy showed 52% plasma cells [Figure 4]. Skin biopsy showed only necrotic material.
Figure 1: Multiple digital gangrenous lesions over both feet (a– c) and post-treatment photographs (d– f) .

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Figure 2: Cryoglobulin precipitates and serum protein electrophoresis showing monoclonal gammopathy .

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Figure 3: Radiographs of the skull and pelvis showing lytic lesions .

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Figure 4: Bone marrow showing plasmacytosis with Leishmans staining, ×100 magnification.

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A diagnosis of multiple myeloma with type 1 cryoglobulinemia was made and the patient was started on chemotherapy with dexamethasone, cyclophosphamide, and bortezomib. On his follow-up visit after 2 months, he was afebrile, joint pain had reduced, and the skin lesions had subsided [Figure 1]d-f.


  Discussion Top


Cryoglobulins are either immunoglobulins, or a mix of immunoglobulin and complement, that precipitate at temperatures less than 37°C and redissolve upon warming. Clinical manifestations are due to ischemic and vasculitic phenomena, including skin lesions, arthritis, artharalgias, reynaud's phenomenon, and mucosal involvement [4].

On the basis of the clonality of the immunoglobulins, cryoglobulins may be subdivided into three [5]. Type 1 cryoglobulinemia is usually seen in association with a hematological malignancy such as chronic lymphocytic leukemia, multiple myeloma, or Waldenström's macroglobulinemia and involves a monoclonal immunoglobulin. Type 2 cryoglobulinemia is usually seen with chronic infections, commonly chronic hepatitis C, and has mixed monoclonal and polyclonal elements. Type 3 cryoglobulinemia is seen mostly with connective tissue disease and has polyclonal immunoglobulin precipitates.

Type 1 cryoglobulinemia in multiple myeloma can have features such as digital gangrene, diffuse levido reticularis, cutaneous ulcers and gall bladder gangrene as presentations. In the largest series (seven cases) describing the clinical and biological characteristics of type 1 cryoglobulinemia in multiple myeloma, it was found that 71.4% of cases had skin lesions [6]. Cutaneous involvement (necrosis and ulcers) in type 1 cryoglobulinemia can be severe in almost half of the patients [7]. Digital gangrene has several differential diagnosis such as autoimmune, hemetological diseases, infections, etc. Therefore, clinicians should be aware of the possibility of type 1 cryoglobulinemia and an underlying hematological malignancy when evaluating a patient with digital gangrene.

Cryoglobulin testing is considered difficult due to sampling prerequisites. Testing for cryoglobulins is complicated by lack of reference range, standards, and stringency in maintaining testing temperature conditions resulting in high false-negative rates. As a result, cryoglobulin testing is generally underutilized. Identification of cryoprecipitate can be critical for patient care; therefore, correct testing conditions are crucial for reliable cryoglobulin testing. The patient's blood sample should be kept at 37°C initially to avoid premature precipitation of cryoglobulins and thereby decreasing the yield for subsequent identification. This could cause a false-negative result. After warm centrifugation or warm cell precipitation, the clear serum is observed at 4°C for formation of cryoprecipitate. Hence, interpretation of the laboratory results in relation to the clinical manifestations requires a partnership between the clinician and the laboratory specialist to make a correct diagnosis [8].

Treatment for severe type I cryoglobulinemia should include plasmapheresis at onset to achieve a rapid control of the cryoglobulin-related symptoms, and specific multiple myeloma treatment should be introduced at an early stage. Bortezomib and lenalidomide are the most effective therapeutic agents for multiple myeloma in the setting of type 1 cryoglobulinemia [6]. The management and prognosis are based primarily on the underlying etiology, and so a thorough effort must be made to identify it. This case highlights the need to search for of an underlying plasma cell disorder in patients presenting with digital gangrene due to type 1 cryoglobulinemia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Tedeschi A, Baratè C, Minola E, Morra E. Cryoglobulinemia. Blood Rev 2007; 21 :183-200.  Back to cited text no. 1
    
2.
Ferri C, Zignego AL, Pileri SA. Cryoglobulins. J Clin Pathol 2002; 55 :4-13.  Back to cited text no. 2
    
3.
Vacula I, Ambrózy E, Makovník M, Stvrtina S, Babál P, Stvrtinová V. Cryoglobulinemia manifested by gangraene of almost all fingers and toes. Int Angiol 2010; 29 :560-564.  Back to cited text no. 3
    
4.
Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet 2012; 379 :348-360.  Back to cited text no. 4
    
5.
Takada S, Shimizu T, Hadano Y, Matsumoto K, Kataoka Y, Arima Y. et al. Cryoglobulinemia (review). Mol Med Rep 2012; 6 :3-8.  Back to cited text no. 5
    
6.
Payet J, Livartowski J, Kavian N, Chandesris O, Dupin N, Wallet N, et al. Type I cryoglobulinemia in multiple myeloma, a rare entity: analysis of clinical and biological characteristics of seven cases and review of the literature. Leuk Lymphoma 2013; 54 :767-777.  Back to cited text no. 6
    
7.
Terrier B, Karras A, Kahn J-E, Le Guenno G, Marie I, Benarous Let al. The spectrum of type I type 1 cryoglobulinemia: new insights based on 64 cases. Medicine (Baltimore) 2013; 92 :61-68.  Back to cited text no. 7
    
8.
Motyckova G, Murali M. Laboratory testing for cryoglobulins. Am J Hematol 2011; 8:500-502.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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