Heavy chain diseases (HCD) are rare B-cell lymphoproliferative disorders characterized by production of a monoclonal immunoglobulin without a light chain. Three subtypes are known based on the type of monoclonal immunoglobulin produced ie. alpha-heavy chain, gamma-heavy chain and mu-heavy chain disease in order of decreasing frequency. Here we report a case of gamma-heavy chain disease in a previously healthy 48 year old African American man, which demonstrated clinical and pathologic response to treatment with bortezomib and dexamethasone.
The patient was transferred to our institution for work-up of persistent high fever, hypotension and eosinophilia after a thorough negative infectious and rheumatologic work-up spanning two outside hospital admissions. The patient had originally presented with two months of constitutional symptoms and cough refractory to antibiotics and prednisone. His outside hospital admissions were notable for an RCA NSTEMI (an unexpectedly large thrombus was noted on cardiac catheterization), eosinophilia and persistent fevers to 105 degrees Fahrenheit. Imaging studies included a CT torso and tagged WBC scan which were unrevealing but for mild splenomegaly of 15 cm and notably did not show lymphadenopathy, masses or evidence for infection. The fevers transiently abated with an empiric course of steroids but recurred accompanied by shock, which responded to a pulse of high dose methylprednisolone. Ultimately he was felt to have primary adrenal insufficiency without evidence of infiltrative disease on dedicated CT. On presentation to our hospital, his initial labs showed WBC 5. 3 K/uL (83% neutrophils, 10% lymphocytes, 3% monocytes, 4% eosinophils), Hb 11. 2 g/dL, platelets 173 K/uL. Comprehensive chemistry profile was unremarkable. SPEP/IFE of the serum and urine revealed a monoclonal gamma-heavy chain without associated light chain. The total IgG was elevated at 2522 mg/dL, IgA was mildly depressed at 57 mg/dL and IgM was normal at 147 mg/dL; the monoclonal protein itself could not be quantitated; hence, total serum IgG was followed. The patient underwent a bone marrow biopsy and aspiration which showed trilineage hematopoiesis, marked esosinophilia, no evidence of leukemia or lymphoma, 10% CD138+ plasma cells, with the overwhelming majority staining for IgG but not for kappa or lambda. A skeletal survey was negative for lytic lesions. The findings were felt to be consistent with a plasma cell dyscrasia associated gamma-heavy chain disease. The observed eosinophilia was felt to be reactive to the gamma-heavy chain disease as has been previously described.
In the literature, gamma heavy chain disease is reported to most commonly present as a lymphoplasmacytic process and the finding of a plasma cell dyscrasia appears to be an unusual presentation of what is already a rare disease. We decided to tailor the treatment to the finding of a plasma cell dyscrasia. Therefore the patient was started on bortezomib 1. 3 mg/m2 SC D1, 4, 8, 11 and dexamethasone 20 mg PO D1, 2, 4, 5, 8, 9, 11, 12 of a 21 day cycle. His treatment was complicated by paroxysmal atrial tachycardia; a cardiac MRI did not reveal evidence of infiltrative cardiomyopathy. After 4 cycles of bortezomib and dexamethasone, the patient's total IgG had normalized at 1265 mg/dL and though a monoclonal gamma heavy chain was still detected by IFE of the serum and urine, a repeat bone marrow biopsy and aspiration was without morphologic evidence of the heavy chain plasma cell dyscrasia. The patient reported feeling subjectively improved with abatement of his malaise and fatigue and without further episodes of fever. Interestingly, the parameter that most seemed to correlate with his clinical status was eosinophilia which also decreased from a peak of 61% (absolute eosinophil count of 5063/uL) to 8–19% after 4 cycles with bortezomib and dexamethasone. Secondary eosinophilia has been reported in the literature in a subset of gamma HCD patients. The patient further underwent stem-cell mobilization in preparation for auto stem cell transplant with high dose Cytoxan, after which the eosinophilia completely resolved.
There are only approximately 120 cases of gamma HCD described in the literature. To our knowledge, this is the first reported case of plasma cell dyscrasia associated gamma HCD responding to treatment with bortezomib and dexamethasone.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.