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1206 Part IX: Lymphocytes and Plasma Cells Chapter 79: Lymphocytosis and Lymphocytopenia 1207

ultraviolet A irradiation may result in T-lymphocyte lymphopenia, toxoplasmosis, neuroinvasive West Nile disease, progressive multifocal
possibly through destruction of cells circulating through the cutane- leukoencephalopathy, or cryptococcal infections). 155–159 The WHO clas-
ous vasculature. The mechanism by which glucocorticoids cause sifies such patients as having idiopathic CD4+ T lymphocytopenia and
133
lymphocytopenia is not clear, but may be secondary to a glucocorti- severe unexplained HIV-seronegative immune suppression. 123
coid-induced redistribution of lymphocytes in addition to induced cell Several observations have helped understand the pathogenesis
destruction. 134–136 Redistribution also may be responsible for the lym- of idiopathic lymphocytopenia. Lymphocyte-specific kinases (LCKs)
phocytopenia occurring after surgery. 137,138 In thoracic duct drainage, play a key role in initiation of signaling from the T-cell receptor (TCR).
139
the lymphocytes are lost from the body. Platelet or stem cell apheresis TCR activates LCK through the adaptor protein, uncoordinated 119
160
similarly lowers the lymphocyte count because of inadvertent removal (UNC119). Consequently a mutation of human UNC119 impairs
of lymphocytes with the platelets. 140 LCK activation resulting in diminished T-cell responses to TCR stimu-
lation and clinically manifests as lymphopenia and opportunistic infec-
Systemic Disease Associated with Lymphocytopenia tions. A heterozygous mutation of UNC119 has been noted in patients
161
Patients with systemic autoimmune disease can have lymphocytope- with Idiopathic CD4+ T-lymphocytopenia. IL-7 and IL-2 signaling
nia, secondary to either the underlying disease or therapy. Patients have been shown to be impaired in this condition, which may explain
162
who present with systemic lupus erythematosus may have autoanti- for the loss of CD4+ T-lymphocyte homeostasis. The exact propor-
body-mediated lymphocytopenia prior to therapy and the presence of tion of patients with this disorder is unknown because patients who are
antilymphocyte antibodies was independently associated with disease not affected clinically by the isolated CD4+ T-cell depletion may not
141
activity and lupus nephritis. Similarly, patients with primary Sjögren come to medical attention. In conclusion, idiopathic CD4+ T lympho-
syndrome sometimes have lymphocytopenia even prior to therapy and cytopenia is a heterogeneous condition diagnosed typically in middle
an association between lymphocytopenia and risk of developing lym- age and is associated with multiple opportunistic infections and auto-
phoma has been observed. 142,143 In conditions such as protein-losing immune diseases. Experimental cytokine therapies with IL-2 have been
enteropathy, lymphocytes may be lost from the body. Severe thermal evaluated in these patients. 163
injury may result in profound T-cell lymphopenia secondary to redis-
144
tribution of blood T cells to the tissues. Lymphopenia has also been
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