Lymphopenia (lymphocytes < 1 to 1.5 G/L depending on the definition)

Repeat later

• FBC

Laboratory tests

• FBC with blood film
• CRP
• Serum protein electrophoresis
• Serum immunoglobulins (IgG, IgA, IgM) (if recurrent infections or hypogammaglobulinaemia on electrophoresis)if neededRecurrent infections or hypogammaglobulinaemia on electrophoresis: look for common variable immunodeficiency or lymphoma ^[2]. The Lothian pathway combines immunoglobulins and electrophoresis from the outset ^[3].
• Serum creatinine
• AST
• ALT
• GGT
• Alkaline phosphatase
• Bilirubin
• LDH
• Serum calcium
• HIV serology
• Antinuclear antibodies (ANA)
• Anti-dsDNA antibodies (if antinuclear antibodies positive or signs of lupus)if neededSigns of the lupus group (arthritis, photosensitivity, skin involvement, serositis) or positive antinuclear antibodies: systemic lupus is a cause of lymphopenia ^[2].
• Anti-CCP antibodies (if arthritis or suspected rheumatoid arthritis)if needednon-French guidelineThe Scottish NHS Lothian guide (2024) asks for anti-CCP and antinuclear antibodies when there are signs of lupus, rheumatoid arthritis or another connective tissue disease ^[3]. The French review does not cite rheumatoid arthritis among the causes of lymphopenia ^[2].
• Angiotensin-converting enzyme (if sarcoidosis suspected)if neededLymphadenopathy, splenomegaly or signs suggesting sarcoidosis: lymphopenia there is due to redistribution of lymphocytes to the tissues, and it is a marker of activity ^[2].
• HTLV-1/2 serology (depending on geographical origin)if neededUnexplained chronic lymphopenia: HTLV infection is one of the chronic infections to look for ^[2]. Geographical origin (endemic area) guides the request.
• Serum albumin (if malnutrition suspected)if neededWeight loss, undernutrition, malabsorption: nutritional status is part of the work-up of chronic lymphopenia ^[2].
• Vitamin B12if neededMacrocytosis, undernutrition, alcohol use disorder: folate deficiency could contribute to the lymphopenia ^[2]; the Lothian pathway measures B12 and folate in primary care ^[3].
• Folateif neededMacrocytosis, undernutrition, alcohol use disorder: folate deficiency could contribute to the lymphopenia ^[2]; the Lothian pathway measures B12 and folate in primary care ^[3].
• Plasma zinc (if malnutrition or recurrent infections)if neededUndernutrition, chronic alcohol use disorder, kidney or digestive disease: zinc deficiency is the most frequent cause of impaired lymphocyte production ^[2].
• CD4/CD8 lymphocyte subsets (if lymphopenia persists without cause after these tests)if neededChronic lymphopenia still unexplained after the work-up, or unusual infections: idiopathic CD4 lymphopenia is defined by CD4 < 300/mm³ or < 20% of lymphocytes on two occasions, with no other cause ^[2].

Imaging

• Chest X-ray