30
Figure 3. Diagnosis of Diseases of Immune Dysregulation
3.1 Suspected
immune
dysregulation
syndrome
3.8 Consider
APECED, IPEX,
CD25, ITCH
3.3 Consider
FHL, XLP, or
accelerated
phase of CHS,
GS, or HPS
NO
3.4
Infections,
hypopigmentation?
• 3.1 – A disorder of immune dysregulation is suspected because of some
combination of clinical features in which 1 or more of the following are prominent:
(1) autoimmunity, (2) hypersensitivity, and (3) signs of lymphoproliferation, such
as diffuse lymphadenopathy, hepatosplenomegaly, or both.
• 3.2 – Does the patient have an acute or fulminant presentation with high
fever, toxic appearance, and signs of lymphoproliferation? Alternatively, if the
presentation is subacute or chronic, are features of recurrent infections and
pigmentary abnormalities present?
• 3.3 – Either of the presentations in 3.2 is consistent with a form of HLH, either FHL
or in association (as an ''accelerated phase'') with another syndrome, such as CHS,
GS, or HPS.
• 3.4 – Are lymphoproliferation and autoimmune disease prominent in the
presentation?
• 3.5 – The presentation in 3.4 suggests ALPS, ALPS-related disorders, or XLP.
• 3.6 – Are any of these features present: (1) polyendocrine autoimmunity,
(2) CMCC, or (3) multiple food and/or environmental allergies?
• 3.7 –The presentation in 3.6 indicates possible APECED, IPEX, or defects of CD25
or ITCH. If none of these diagnoses is correct, the patient might have a CID or
syndrome. Consider evaluation as outlined in Figure 2.
3.2 Acute/toxic
presentation, high
fever, lymphadenopathy,
hepatosplenomegaly?
3.6
Consider
ALPS and
related
conditions,
XLP
3.9 Consider
alternative
diagnosis
NO
YES
YES
3.5
Lymphadenopathy,
hepatosplenomegaly,
autoimmunity?
NO
NO
YES
3.7
Polyendocrine
autoimmunity,
candidiasis, or food and
environmental
allergy?
YES
Diseases of Immune Dysregulation
