Catalytic Health

8 Volume 3, Issue 1, May, 2023 connective tissue and plays a role in TH2 mediated pruritus and autoimmune disease. 8 This molecular change is produced by a variety of leukocytes including T cells, eosinophils, basophils, mast cells, monocytes and dendritic cells. 10 In malignancy, there is an increase in pruritogens. For example, mast cells in patients with myeloproliferative disorders release more histamine, leukotrienes and IL-31 compared to those of healthy individuals. 11 In other hematologic malignancies, the cancer cell itself can release histamine, leukopeptidases, bradykinins and IL-31. Additionally, numerous hematologic malignancies can visually involve the skin leading to discomfort, either alone or in combination with systemic disease. When to consider hematologic malignancy as the cause of pruritus Table 1 outlines various hematologic diagnoses associated with pruritus. Generalized pruritus is seen in only 1%-3% of patients with non-Hodgkin lymphoma, but in up to 19%-30% of those with Hodgkin lymphoma, 12, 13 occurring more often in the nodular sclerosis subtype. Itch can precede the clinical onset of lymphoma, sometimes described as a burning quality occurring at night, or even precipitated by alcohol consumption. Mycosis fungoides and Sezary syndrome are cutaneous hematologic malignancies associated with itch and rash. A skin biopsy can be helpful in these cases. Aquagenic pruritus, a hot bath- or shower-induced itch, is described in 30%-40% of individuals with a myeloproliferative neoplasm called polycythemia vera (PV). These patients may also present with abdominal symptoms and should have a detailed thromboembolic history as they are at risk of venous and arterial thromboembolism There are no accepted screening tests for hematologic malignancies. However, routine bloodwork abnormalities may be uncovered. There is a wide spectrum of presentations of hematologic malignancies, ranging from an incidental finding on imaging or routine blood work to an aggressive symptomatic presentation. A symptomatic presentation can include enlarged lymph nodes, symptoms of a mediastinal mass including new cough or shortness of breath, symptoms of splenomegaly including early satiety or abdominal fullness, or constitutional symptoms including recurrent fevers, drenching night sweats or unintended weight loss. A physical examination with specific palpation of cervical, axillary and inguinal lymph nodes regions, and abdominal examination for enlargement of the spleen and liver is recommended. If history and physical exam are suspicious, or if there has been no cause found, a complete blood count (CBC) and lactate dehydrogenase (LDH) can be helpful. For example, PV is characterized by high hemoglobin levels and can be identified on a CBC. Thrombocythemia can result from reactive or inflammatory causes or relating to a specific mutation such as with the myeloproliferative neoplasms. Some hematologic malignancies such as Hodgkin lymphoma can result in a reactive leukocytosis, predominantly displaying as a left shift or neutrophilia, while some patients may have malignant cells circulating that can be detected on their leukocyte differential. If there is suspicion for hematologic malignancy with a lymphocytosis or abnormal blood cells such as blasts present, flow cytometry testing can be sent on a peripheral blood sample to examine for clonal malignant populations. This test is not useful in the setting of reactive neutrophilia alone, and a blood smear review may help guide decision making. The LDH test can be helpful if elevated and is frequently used in prognostic scores for hematologic malignancy, but should be interpreted with caution as a non-specific test for tissue turnover. If lymphadenopathy is present on exam, consideration should be given to CT or ultrasound imaging, depending on location and other patient factors, such as risk for contrast induced injury, radiation exposure and others. The largest and most easily accessible node should be targeted for an excisional (surgical) or core biopsy (interventional radiology or surgical). Fine needle aspirates are inadequate for pathological confirmation of a lymphoproliferative disorder, necessitating a second biopsy and resulting in a delay in diagnosis and treatment. This should be sent specifically for "lymphoma protocol" or the local correlate, such that part of the tissue is saved fresh for flow cytometry testing. In the case of concern for hepatosplenomegaly, abdominal ultrasound can be performed. If concerns remain from initial workup, then referral to a hematology specialist should occur. Figure 2 summarizes an initial approach to the work- up of suspected hematologic malignancy in the patient who presents with pruritus. During the course of workup, providers may wish to treat the unpleasant symptom of pruritus. While first line therapy remains topical treatments (i.e., corticosteroids), emollients and anti-histamines, other therapies with varying efficacy for refractory pruritus can be considered. These include gabapentin, mirtazapine, and SSRIs. A systematic review of itch

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