What is the next step for a patient with pruritus (itching) of the extremities causing bruising, unresponsive to hydroxyzine (Vistaril), with normal platelet count and prothrombin time/international normalized ratio (PT/INR), and a history of vitamin B12 deficiency?

Next Step: Comprehensive Laboratory Workup for Hematological and Systemic Causes

Order a complete blood count with peripheral blood smear, ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), liver function tests, and renal function tests immediately to evaluate for hematological malignancies (particularly lymphoma), polycythemia vera, and iron deficiency—all of which are critical causes of treatment-refractory pruritus. 1, 2, 3

Why This Workup Is Essential

The combination of extremity pruritus causing bruising (from scratching), failure to respond to hydroxyzine, and a history of B12 deficiency raises significant concern for underlying hematological disease. 2

• Hematological disorders account for approximately 2% of generalized pruritus cases but are among the most serious and treatable causes. 1, 2
• The British Association of Dermatologists specifically recommends this systematic evaluation for patients with pruritus unresponsive to antihistamines. 1, 3

Specific Red Flags to Assess

Clinical History Details to Elicit Now:

• Nocturnal predominance of itching, weight loss, fever, or night sweats strongly suggests Hodgkin lymphoma. 1, 2
• Water-induced pruritus (aquagenic pruritus) is highly characteristic of polycythemia vera. 1, 2
• Palpable lymph nodes or masses require urgent biopsy referral. 1

Physical Examination:

• Examine for lymphadenopathy or masses that would necessitate immediate biopsy. 1, 2
• Assess for hepatosplenomegaly suggesting myeloproliferative disorders. 1

Interpretation of Laboratory Results

If Elevated Hemoglobin/Hematocrit:

• Order JAK2 V617F mutation testing immediately, as it is present in up to 97% of polycythemia vera cases. 1, 2
• Look for microcytosis (suggesting secondary iron deficiency from polycythemia vera), elevated white cell or platelet count, and low ESR. 1
• Refer to hematology urgently. 1, 2

If Low Ferritin or Microcytic Anemia:

• Iron deficiency causes pruritus in 25% of patients with systemic pruritus and responds to iron replacement. 2, 3
• Initiate therapeutic trial with iron supplementation if ferritin is below the lower limit of normal. 2
• Critical caveat: Ferritin is an acute-phase reactant and may be falsely "normal" in inflammatory states; if clinical suspicion remains high, check serum iron and total iron-binding capacity. 2

If Elevated LDH, Abnormal Blood Film, or Elevated ESR:

• These findings suggest lymphoma or other hematological malignancy. 1, 2
• Refer to hematology for bone marrow biopsy or lymph node biopsy. 1, 2

Symptomatic Management While Awaiting Results

While completing the diagnostic workup, initiate symptomatic treatment:

• Liberal emollients to restore skin barrier function. 2
• Non-sedating antihistamines (fexofenadine or loratadine) may be tried, though efficacy is limited in non-histaminergic pruritus. 2
• Avoid sedating antihistamines (like hydroxyzine long-term) due to dementia risk with prolonged use. 2
• Consider topical doxepin for localized symptomatic relief. 2

When to Refer to Specialists

Immediate Hematology Referral If:

• Elevated hemoglobin/hematocrit suggesting polycythemia vera. 1, 2
• Abnormal blood film, elevated LDH, or clinical features suggesting lymphoma. 1, 2
• Palpable lymphadenopathy or masses. 1, 2

Dermatology Referral If:

• Pruritus persists despite primary care management and negative initial workup. 2
• Consider skin biopsy from the trunk if persistent unexplained pruritus, as cutaneous lymphoma can present with normal-appearing skin. 1, 2

Common Pitfalls to Avoid

• Do not order routine thyroid function tests unless there are specific clinical features suggesting thyroid disease; endocrine causes are rare. 1, 3
• Do not pursue extensive malignancy screening without specific clinical indicators beyond pruritus alone. 1, 3
• Do not overlook medication review—drug-induced pruritus is common and reversible. 2
• Do not assume normal platelets and PT/INR rule out hematological disease—lymphoma and polycythemia vera can present with normal coagulation studies. 1