|Year : 2014 | Volume
| Issue : 3 | Page : 107-110
Multiple myeloma presenting as extensive limb gangrene
Mansoor C Abdulla1, Lekha K Nair2, Ram Narayan1, Anitha Das2
1 Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala, India
2 Department of Pathology, M.E.S. Medical College, Perinthalmanna, Kerala, India
|Date of Web Publication||30-Sep-2014|
Mansoor C Abdulla
Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala
Source of Support: None, Conflict of Interest: None
Cryoglobulinemic vasculitis is one of the rare manifestations of plasma cell dyscrasias. A 54-year-old diabetic housewife presented with pain and blackish discoloration of her right foot and medial four fingers of the right hand. She underwent transmetatarsal amputation of her right and left feet due to digital gangrene 1 year and 9 months back respectively. On diagnostic evaluation, she was found to have multiple myeloma with cryoglobulinemic vasculitis. This case report emphasizes the importance of considering the possibility of cryoglobulinemic vasculitis and underlying plasma cell dyscrasias in patients presenting with gangrene of extremity.
Keywords: Cryoglobulinemic vasculitis, gangrene, multiple myeloma
|How to cite this article:|
Abdulla MC, Nair LK, Narayan R, Das A. Multiple myeloma presenting as extensive limb gangrene. J Appl Hematol 2014;5:107-10
| Introduction|| |
Cryoglobulinemia is classified to three subtypes.  Type I cryoglobulins account for 10-15% of all cryoglobulinemias and are found in patients with hematological disorders,  commonly with plasma cell dyscrasias such as multiple myeloma or Waldenstrom macroglobulinemia.  The cutaneous manifestations of cryoglobulinemia include palpable purpura, livedo reticularis, ischemic necrosis, and cutaneous ulcerations.  Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels.  In this report, we describe a patient who presented with gangrene of three limbs, underwent multiple amputations and found to have cryoglobulinemic vasculitis due to multiple myeloma as the underlying cause.
| Case report|| |
A 54-year-old housewife who had a fracture of her right humerus on attempting to get up from a sitting posture was admitted under our care 2 days following the fracture with pain and blackish discoloration of her right foot and medial four fingers of the right hand. She was taking medications for diabetes and hypertension for 8 and 3 years, respectively. Previously, she had undergone a transmetarsal amputation 1 year ago due to gangrene of all toes on the right foot. Evaluation at that time did not reveal any obvious cause for the gangrene. Transmetarsal amputation had been done 9 months earlier on the left foot for digital gangrene of all the toes.
On examination, she was pale and her blood pressure was 140/90 mm of Hg. She had gangrene of the medial four fingers of her right hand [Figure 1] and right foot [Figure 2] extending up to the forefoot. Multiple blisters, ulcers and blackish discoloration were present over the right hip. Systemic examination did not reveal any abnormalities.
Investigations showed hemoglobin = 7.3 g/dl (microcytic hypochromic), total white blood cell count 10,900/μl, platelet count 2.1 × 10 9 /L, erythrocyte sedimentation rate 165 mm in 1 h, prothrombin time = 24.4 s, partial thromboplastin time = 32 s and an international normalized ratio of 1.71. Urinalysis showed 1 + albuminuria with 2-4 leucocytes/high power fields. Chest X-ray and electrocardiogram were normal. Her biochemical parameters revealed random blood sugar = 165 mg%, urea = 34 mg/dl, creatinine = 0.7 mg/dl, sodium = 144 mmol/L, potassium = 4.1 mmol/L, aspartate aminotransferase = 63 IU/L, alanine transaminase = 13 IU/L, alkaline phosphatase = 138 IU/L, total bilirubin = 0.8 mg/dl, direct bilirubin = 0.1 mg/dl, total protein = 9.1 g/dl, albumin = 3.6 g/dl, globulin = 6.4 g/dl. Peripheral smear showed microcytic hypochromic anemia. Doppler study of both lower and left upper limbs was normal. Her vasculitis workup including antinuclear antibody profile, rheumatoid arthritis, cytoplasmic anti-neutrophil cytoplasm antibodies (ANCA), perinuclear-ANCA, immunoglobulin M (IgM) and IgG anticardiolipin antibodies, hepatitis B surface antigen, hepatitis C virus, HIV, venereal disease research laboratory were all negative.
X-rays of her skull [Figure 3] and pelvis showed multiple lytic lesions and fracture of the right humerus [Figure 4]. Urinary Bence-Jones protein was positive and serum protein electrophoresis revealed monoclonal gammopathy [Figure 5]. Cryoglobulins were detected. Serum protein immunofixation revealed monoclonal gammopathy in IgG, lambda regions and a band of cryoglobulin. Bone marrow trephine biopsy showed 63% plasma cells [Figure 6]. On skin biopsy, the epidermis showed mild hyperkeratosis; the dermis had extensive extravasation of red blood cells [Figure 7]. Blood vessels had homogenous, eosinophilic, jelly like material in the lumen with minimal chronic inflammatory infiltrate around blood vessels [Figure 8]. Luminal material was found positive for periodic acid-Schiff staining [Figure 9] suggestive of cryoglobulinemic vasculitis. Based on the aforementioned investigations, she was diagnosed to have multiple myeloma with cryoglobulinemic vasculitis.
|Figure 6: Bone marrow showing plasmacytosis with Leishman's staining, ×100|
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|Figure 7: Skin biopsy showing extensive extravasation of red blood cells with H and E, ×4|
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|Figure 8: Homogenous eosinophilic material in vessel lumen with H and E, ×40|
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|Figure 9: Periodic acid-Schiff positivity for the material in vessel lumen with periodic acid-Schiff staining, ×10|
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She was started on plasmapheresis (3 L/day). Chemotherapy for multiple myeloma was initiated with dexamethasone, cyclophosphamide and bortezomib. However, she developed a severe pneumonia with renal failure and succumbed to her illness.
| Discussion|| |
Cryoglobulins are serum immunoglobulins that precipitate in temperatures <37°C and redissolve upon warming. Hyperviscosity and/or immune-mediated vasculitis can result in multi-organ damage. Clinical manifestations are therefore myriad with ischemic and/or vasculitic phenomena such as skin lesions,  arthritis, artharalgias, Reynaud's phenomeneon, and mucosal involvement. 
Various case-reports regarding cryoglobulinemia in multiple myeloma have reported finger gangrene, diffuse livedo reticularis,  cutaneous ulcers and gall bladder gangrene as the presentations.  However, extensive gangrene of all the four limbs due to cryoglobulinemia has rarely been reported. ,, Our patient presented with gangrene involving three limbs which is a very rare presentation of Type I cryoglobulinemia associated with multiple myeloma.
Our patient had a history of digital gangrene in the past for which she was evaluated extensively. Digital gangrene itself has several differential diagnosis such as autoimmune, hematological diseases, infections, etc.  She was diagnosed to have multiple myeloma with cryoglobulinemia only after she developed a pathological fracture of the humerus. Hence, clinicians should be aware of the possibility of cryoglobulinemia and an underlying hematological malignancy, while evaluating a patient with limb gangrene.
The management and prognosis are based primarily on the underlying etiology, so a thorough effort must be made to identify the basic abnormality.  Cryoglobulin testing is perceived as exasperating and difficult due to sampling prerequisites. There is also significant interlaboratory and intralaboratory variation in storage and testing. As a result, cryoglobulin testing is generally underutilized.
| Conclusion|| |
We report a case of multiple myeloma with a very rare presentation of extensive limb gangrene as a result of vasculitis due to Type I cryoglobulinemia. Our case report reminds readers to be aware of this rare entity when evaluating patients with limb gangrene.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]