Intravascular Crystal Deposition: An Early Clue to Diagnosing Type 1 Cryoglobulinemic Vasculitis
Bryan Gammon, MD,* Michelle Longmire, MD,† and Brittney DeClerck, MD*†
Dermatopathology Research Introduction
Cutaneous small vessel vasculitis (CSVV) is a condition with a broad differential diagnosis. While many cases are benign and limited to the skin, it is crucial to distinguish these from severe systemic vasculitides that can present with similar skin findings in dermatopathology. Approximately half of patients with systemic vasculitis experience skin involvement at some stage. Notably, CSVV involving both superficial and deep dermal vessels is more commonly associated with systemic disease than CSVV limited to superficial vessels.
However, distinguishing between CSVV and systemic vasculitis can be challenging. In some cases, up to 43% of patients with CSVV develop renal disease related to conditions like Henoch-Schönlein purpura, microscopic polyangiitis, or Wegener granulomatosis, classifying vasculitis based on vessel size and depth of involvement helps narrow down the differential diagnosis. Direct immunofluorescence and antineutrophil cytoplasmic antibody assays are also essential in this process. Despite these measures, determining which patients with CSVV are at risk for systemic disease remains challenging. Early diagnosis and treatment are critical to prevent further vascular and organ damage, which could be fatal.
Methods and Materials
Biopsy specimens were fixed in 10% buffered formalin, processed routinely, and embedded in paraffin. Additionally, serial 4-μm-thick sections were cut for hematoxylin and eosin staining.
Type 1 Cryoglobulinemic Vasculitis Case Report
Sixteen years prior to this report, a 56-year-old white female had a significant medical history of hypothyroidism, hypertension, and monoclonal gammopathy of undetermined significance. However, during this case, her diagnosis was presented with painful erythematous to purpuric papules on her distal digits, initially involving the right foot and then spreading to both feet and the left hand. The patient also reported progressive upper back pain over the week before admission.
On examination, she had retiform purpura on the forefoot and toes, and purpuric periungual papules on the left hand. Also, a punch biopsy of the right third toe showed an unremarkable epidermis, superficial and deep mixed perivascular infiltrate, and fibrin thrombi in small dermal blood vessels. We also observed prominent leukocytoclastic vasculitis, along with polygonal nonpolarizable eosinophilic crystals within the vascular lumen of several vessels. Direct immunofluorescence showed intravascular and perivascular immunoglobulin G (IgG), C3, and fibrinogen.
IMAGE 1
The patient presented with a 1-week history of painful erythematous to violaceous papules and retiform patches on the bilateral dorsal feet and left hand.
Laboratory tests revealed a negative HIV, viral hepatitis, antinuclear antibody, and rheumatoid factor assays. The patient had mild macrocytic anemia, moderate polychromasia, and occasional rouleaux formation on a peripheral blood smear. In addition, elevated total protein and serum globulin levels, along with a serum cryoprotein level of 17%, were noted. A serum-free light chain assay showed elevated free kappa light chain levels. Serum protein electrophoresis identified a monoclonal IgG band, and a bone marrow biopsy confirmed plasma cell myeloma with 20% kappa-restricted plasma cells.
Dermatopathology IMAGE 2
A punch biopsy of the right third toe demonstrates a superficial and deep perivascular infiltrate. A: Fibrin thrombi were noted within the lumen of small dermal blood vessels (×40). B: Higher power examination revealed prominent leukocytoclastic vasculitis, characterized by hemorrhage, fibrin deposition, nuclear debris, as well as transmural migration of neutrophils (×200). C: Polygonal eosinophilic crystals were also noted within the vascular lumen of several vessels (×600).
The patient was diagnosed with IgG kappa multiple myeloma complicated by type 1 cryoglobulinemic vasculitis. Therefore, she was treated with high-dose corticosteroids and cytotoxic chemotherapy, including dexamethasone, bortezomib, and cyclophosphamide.
Case Discussion of Type 1 Cryoglobulinemia
Though a rare cause of vasculitis, type 1 cryoglobulinemia is typically associated with B-cell lymphoproliferative disorders. Unlike mixed cryoglobulinemia, which is often linked to the hepatitis C virus and features polyclonal immunoglobulins, this condition involves monoclonal immunoglobulins. It also usually results in more severe skin involvement. Early diagnosis and aggressive chemotherapy are crucial to prevent further vessel and organ damage.
Overall, immunoglobulin crystal formation is a key indicator of an underlying plasma cell dyscrasia. Crystals have been reported in various tissues, including peripheral blood, joints, ascitic fluid, and bowel resection specimens, often in the absence of detectable cryoglobulins. Intravascular crystal formation in CSVV, as seen in this case, has not been previously reported and may serve as an early diagnostic clue for underlying plasma cell dyscrasia in patients presenting with CSVV.
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