You have been logged out of VisualDx or your session has expired.

Please reload this page and sign into VisualDx to continue.

  VisualDx Mobile   Select Language

Get VisualDx Mobile

There are VisualDx mobile apps available for iOS and Android devices.

You will need a VisualDx account to use the mobile apps.

Already have an account? Sign In or
sign up for a free trial.

Users with VisualDx accounts earn CME credits for using VisualDx.

Already have an account? Sign In or
sign up for a free trial.

Create a Personal Account

E-mail (username)
Verify Password
First Name
Last Name

Personal Account Created

Mobile Access

You can now download VisualDx for your iOS and Android devices. Launch the VisualDx app from your device and sign in using your VisualDx personal account username and password.

CME Certification

Sign in with your personal account to earn and claim CME credits through VisualDx. Credits can be earned by building a differential or looking up a diagnosis.

Version: 7.11.1423   (build b7dc603)
Select Language

Select Region

Send us your feedback

This field is required

Oops! There was an issue during submission. Please try again. If the problem persists, email with your feedback.

Thank You!

We appreciate your feedback and you will be hearing from us soon.


Share This Page

Thank You!

We have sent an e-mail with a link to the current page.


E-mail This Patient Information Sheet

Thank You!

We have sent an e-mail with this patient information.


Image Contributors


  • Christine Ahn MD
    Carl Allen DDS, MSD
    Brandon Ayres MD
    Howard P. Baden MD
    Robert Baran MD
    Keira Barr MD
    Gregory J. Basura MD, Ph.D
    Donald Belsito MD
    Jeffrey D. Bernhard MD
    Jesse Berry MD
    Victor Blanco MD
    Benjamin R. Bohaty MD
    William Bonnez MD
    Sarah Brenner MD
    Robert A. Briggaman MD
    Robert Brodell MD
    Roman Bronfenbrener MD
    Walter Brooks MD
    William Buckley MD
    Philip Bulterys MD, PhD (candidate)
    Susan Burgin MD
    Sonya Burton MD
    Sean P. Bush MD, FACEP
    Jeffrey Callen MD
    Scott Camazine MD
    Michael Cardwell
    Shelley D. Cathcart MD
    Robert Chalmers MD, MRCP, FRCP
    Chia-Yu Chu MD, PhD
    Flavio Ciferri MD
    Maria Rosa Cordisco MD
    Noah Craft MD, PhD
    John T. Crissey MD
    Harold E. Cross MD, PhD
    Charles Crutchfield III MD
    Adriana Cruz MD
    Donna Culton MD, PhD
    Bart J. Currie MBBS, FRACP, DTM&H
    Chicky Dadlani MD
    Alexander Dane DO
    C. Ralph Daniel III MD
    Thomas Darling MD, PhD
    William Delaney MD
    Damian P. DiCostanzo MD
    Ncoza Dlova MD
    James Earls MD
    Libby Edwards MD
    Melissa K. Egge MD
    Charles N. Ellis MD
    Rachel Ellis MD
    David Elpern MD
    Nancy Esterly MD
    Stephen Estes MD
    E. Dale Everett MD
    Janet Fairley MD
    David Feingold MD
    Benjamin Fisher MD
    Henry Foong MBBS, FRCP
    David Foster MD, MPH
    Brian D. Foy PhD
    Michael Franzblau MD
    Vincent Fulginiti MD
    Sunir J. Garg MD, FACS
    Kevin J. Geary MD
    Lowell Goldsmith MD, MPH
    Sethuraman Gomathy MD
    Bernardo Gontijo MD, PhD
    Kenneth Greer MD
    Kenneth G. Gross MD
    Alan Gruber MD
    Nathan D. Gundacker MD
    Akshya Gupta MD
    Vidal Haddad MSC, PhD, MD
    Edward Halperin MD, MA
    Ronald Hansen MD
    John Harvey
    Rizwan Hassan MD
    Michael Hawke MD
    Jason E. Hawkes MD
    Peter W. Heald MD
    David G. Hicks MD
    Sarah Hocker DO
    Ryan J. Hoefen MD, PhD
    Li-Yang Hsu MD
    William Huang MD
    Sanjana Iyengar MD
    Alvin H. Jacobs MD
    Saagar Jadeja MD
    Shahbaz A. Janjua MD
    Joshua J. Jarvis MD
    Kit Johnson
    Robert Kalb MD
    A. Paul Kelly MD
    Henry Kempe MD
    Loren Ketai MD
    Sidney Klaus MD
    Ashwin Kosambia MD
    Jessica A. Kozel MD
    Carl Krucke
    Mario E. Lacouture MD
    Joseph Lam MD
    Alfred T. Lane MD
    Edith Lederman MD
    Nahyoung Grace Lee MD
    Pedro Legua MD, PhD
    Robert Levin MD
    Bethany Lewis MD
    Sue Lewis-Jones FRCP, FRCPCH
    Taisheng Li MD
    Christine Liang MD
    Shari Lipner MD, PhD
    Adam Lipworth MD
    Jason Maguire MD
    Mark Malek MD, MPH
    Jere Mammino DO
    Ricardo Mandojana MD
    Lynne Margesson MD
    Thomas J. Marrie MD
    Maydel Martinez MD
    Ralph Massey MD
    Patrick McCleskey MD
    Karen McKoy MD
    Thomas McMeekin MD
    Josette McMichael MD
    Somchai Meesiri MD
    Joseph F. Merola MD
    Mary Gail Mercurio MD
    Anis Miladi MD
    Larry E. Millikan MD
    Dan Milner Jr. MD
    Zaw Min MD
    Stephanie Montero
    Alastair Moore MD
    Keith Morley MD
    Dean Morrell MD
    Samuel Moschella MD
    Taimor Nawaz MD
    Vic Newcomer MD
    John Nguyen MD
    Matilda Nicholas MD
    Thomas P. Nigra MD
    Steven Oberlender MD, PhD
    Maria Teresa Ochoa MD
    Art Papier MD
    Lawrence Parish MD
    Tanner Parrent MD
    Mukesh Patel MD
    Lauren Patty-Daskivich MD
    David Peng MD, MPH
    Robert Penne MD
    Nitipong Permpalung MD
    Miriam Pomeranz MD
    Doug Powell MD
    Harold S. Rabinovitz MD
    Christopher J. Rapuano MD
    Sireesha Reddy MD
    Angela Restrepo MD, PhD
    Bertrand Richert MD, PhD
    J. Martin Rodriguez, MD, FACP
    Theodore Rosen MD
    Misha Rosenbach MD
    Scott Schiffman MD
    Robert H. Schosser MD
    Glynis A. Scott MD
    Carlos Seas MD, MSc
    Deniz Seçkin MD
    Daniel Sexton MD
    Paul K. Shitabata MD
    Tor Shwayder MD, FAAP, FAAD
    Elaine Siegfried MD
    Gene Sienkiewicz MD
    Christye Sisson
    Philip I. Song MD
    Mary J. Spencer MD, FAAP
    Lawrence B. Stack MD
    Sarah Stein MD
    William Van Stoecker MD
    Frances J. Storrs MD
    Erik J. Stratman MD
    Lindsay C. Strowd MD
    Erika Summers MD
    Belinda Tan MD, PhD
    Robert Tomsick MD
    Hensin Tsao MD, PhD
    Jenny Valverde MD
    Vishalakshi Viswanath MD
    Susan Voci MD
    Lisa Wallin ANP, FCCWS
    Douglas Walsh MD
    Ryan R. Walsh MD
    George Watt MD
    Clayton E. Wheeler MD
    Sally-Ann Whelan MS, NP, CWOCN
    Jan Willems MD, PhD
    James Henry Willig MD, MPH
    Karen Wiss MD
    Vivian Wong MD, PhD
    Sook-Bin Woo MS, DMD, MMSc
    Jamie Woodcock MD
    Stephen J. Xenias MD
    Lisa Zaba MD
    Vijay Zawar MD
    Bonnnie Zhang MD
    Carolyn Ziemer MD


  • Am. Journal of Trop. Med & Hygiene
  • Armed Forces Pest Management Board
  • Blackwell Publishing
  • Bugwood Network
  • Centers For Disease Control and Prevention
  • Centro Internacional de Entrenamiento e Investigaciones Mèdicas (CIDEIM)
  • Dermatology Online Journal
  • East Carolina University (ECU), Division of Dermatology
  • International Atomic Energy Agency
  • Massachusetts Medical Society
  • Oxford University Press
  • Radiological Society of North America
  • Washington Hospital Center
  • Wikipedia
  • World Health Organization
ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyReferencesView all Images (6)
Congenital agammaglobulinemia - Skin
Other Resources UpToDate PubMed

Congenital agammaglobulinemia - Skin

Print Images (6)
Contributors: Arin Isenstein MD, David Dasher MD, Jeffrey D. Bernhard MD, Craig N. Burkhart MD, Dean Morrell MD, Lowell A. Goldsmith MD, MPH, Nancy Esterly MD
Other Resources UpToDate PubMed


Agammaglobulinemia is a primary immunodeficiency in which B-cell development fails, leading to lack of circulating B-cells and hypogammaglobulinemia. This condition is most commonly inherited in an X-linked fashion and is known as X-linked agammaglobulinemia or Bruton's agammaglobulinemia.

X-linked agammaglobulinemia is rare; the incidence is reported to be 1 per 250,000 live births in the United States. There is no known difference in frequency of this condition among various ethnic or racial groups, although diagnosis may be delayed in patients of color because skin lesions may be more difficult to discern in darkly pigmented skin. Female carriers do not manifest clinical disease because of selective inactivation of the abnormal X chromosome in B-cells.

X-linked agammaglobulinemia results from a mutation in the gene for Bruton's tyrosine kinase (BTK), found on the X chromosome. BTK is a nonreceptor cytoplasmic tyrosine kinase involved in B-cell receptor intracellular signaling, development, and differentiation. Loss-of-function mutations in BTK result in lack of mature B-cells and immunoglobulins of all classes. Fifty percent of the mutations are new, and these patients do not have a family history of the condition.

Less commonly agammaglobulinemia is inherited in an autosomal recessive fashion and is referred to as autosomal recessive agammaglobulinemia. Autosomal recessive agammaglobulinemia is rare and constitutes at most 10-15% of patients with agammaglobulinemia. Males and females are affected equally. In these cases, B-cell development fails because of mutations in multiple genes encoding mu heavy chain, immunoglobulin lambda-like-1 polypeptide, B-cell linker protein, and CD 79a.

Patients with autosomal recessive agammaglobulinemia and X-linked agammaglobulinemia present similarly. Typically patients develop recurrent pyogenic infections between 6 months to 1 year of age, when maternal antibodies passed transplacentally disappear. These patients are susceptible to encapsulated organisms, most commonly Streptococcus pneumoniae, Haemophilus influenzae type B, and Staphylococcus. Sinopulmonary infections including otitis media, sinusitis, and pneumonia are most common, followed by skin infections, gastrointestinal infections, sepsis, meningitis, and osteomyelitis.

Patients with agammaglobulinemia handle fungal and viral infections normally except for enteroviruses; patients with agammaglobulinemia can develop meningoencephalitis and a dermatomyositis-like syndrome from systemic enterovirus infection. The most common enterovirus involved is echovirus followed by coxsackie virus and polio virus from live vaccine. Consequently, affected patients should avoid live polio vaccine. With regard to protozoa, patients with agammaglobulinemia are at increased risk for Giardia infection causing gastroenteritis.

In addition to infections, patients with agammaglobulinemia develop noninfectious skin and joint conditions. These patients can have an atopic dermatitis-like eczematous eruption that is not infectious. Rarely, pyoderma gangrenosum and noninfectious cutaneous granulomas have been reported in patients with agammaglobulinemia.
Twenty percent of patients develop a monoarticular nonseptic arthritis of large joints that may be confused with juvenile rheumatoid arthritis.

Patients with agammaglobulinemia are not at increased risk for autoimmune diseases, unlike patients with common variable immunodeficiency syndrome. The risk of lymphoreticular malignancies may be as high as 6%, and colorectal malignancies have been reported in patients with X-linked agammaglobulinemia. Failure to thrive is not commonly seen in affected patients aside from subsets that have growth hormone deficiency or develop bronchiectasis from recurrent pulmonary infections. When treatment with intravenous immunoglobulin (IVIG) is started before the age of 5, patients do better and have fewer infections. The exact life expectancy of these treated patients is not known but is thought to be at least into the 6th decade.

For more information on X-linked agammaglobulinemia, see OMIM.

For more information on autosomal recessive agammaglobulinemia, see OMIM.


D80.0 – Hereditary hypogammaglobulinemia

116133005 – Congenital agammaglobulinemia

Look For

Subscription Required

Diagnostic Pearls

Subscription Required

Differential Diagnosis & Pitfalls

  • Atopic dermatitis – not associated with recurrent sinopulmonary infections
  • Chronic granulomatous disease – recurrent skin abscesses with bacteria, fungi, and atypical mycobacteria; normal immunoglobulin levels
  • Common variable immunodeficiency – recurrent bacterial infections, autoimmunity, and splenomegaly; often adult onset; low quantitative immunoglobulin levels and abnormal cellular immunity
  • Elevated IgM with hypogammaglobulinemia – recurrent sinopulmonary and gastrointestinal infections, oral ulcerations, and verrucae; increased IgM
  • Ectodermal dysplasia with immunodeficiency – hypotrichosis, hypohidrosis, and hypo/anodontia; recurrent bacterial, viral, and atypical mycobacterial infections
  • Severe combined immunodeficiency – bacterial, viral, and fungal infections; abnormal humoral and cellular immunity
  • Wiskott-Aldrich syndrome – atopiform dermatitis, recurrent pyogenic infections, thrombocytopenia, platelet dysfunction, and increased risk of lymphoreticular malignancy

Best Tests

Subscription Required

Management Pearls

Subscription Required


Subscription Required


Subscription Required

Last Updated: 03/29/2017
Copyright © 2018 VisualDx®. All rights reserved.
Congenital agammaglobulinemia - Skin
Print 6 Images
View all Images (6)
(with subscription)
Congenital agammaglobulinemia : Crust, Hypogammaglobulinemia, Acute otitis media, Non-bullous impetigo, Recurring sinusitis
Clinical image of Congenital agammaglobulinemia
Copyright © 2018 VisualDx®. All rights reserved.