Common Variable Immunodeficiency Clinical Presentation

Updated: Apr 16, 2019
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Five distinct clinical phenotypes have been delineated for common variable immunodeficiency (CVID): no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. [26] In any patient with a past medical history of CVID, 3 complications must be considered: recurrent infections, autoimmune phenomena, and malignancy (see Physical).

Patients with CVID often have a history of recurrent infections.

The recurrent infections commonly affect the upper and lower respiratory tracts. Patients come to medical attention due to infectious diseases at the time of onset, the most common being otitis media, diarrhea, pneumonia, and sinusitis. [28] Almost all have acute and recurrent infections. Infections with unusual organisms, including Prototheca algae infection, may be seen. [29]

Persistent diarrhea and malabsorption caused by Giardia lamblia infection occur in patients with CVID. Symptoms generally resolve after treatment with metronidazole. Infectious and autoimmune etiologies are the most likely causes for severe chronic diarrhea. Diarrhea is not a common symptom of gastrointestinal malignancy.

Young children may fail to thrive because of the frequent infections or gastrointestinal tract disease.

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Physical Examination

Generally, the physical examination findings are correlated to the history, and they depend on the clinical presentation and specific organs involved.

Splenomegaly and generalized lymphadenopathy are present in many patients with common variable immunodeficiency (CVID).

Recurrent infections

Permanent damage to the bronchi may occur, resulting in bronchiectasis.

Common infective organisms include Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus.

In some patients with CVID, uncommon infectious agents such as Pneumocystis carinii and Mycoplasma pneumoniae may be detected first.

In addition to pulmonary infection, M pneumoniae can also cause primary infection in the urinary tract and joints.

Infection with G lamblia may cause persistent diarrhea and malabsorption.

Recurrent infections with herpes simplex virus are reported. Herpes zoster infection may develop in as many as 20% of patients with CVID.

Enterovirus infection has been reported in association with CVID. [30]

Autoimmune phenomena

As many as 20% of patients with CVID develop autoimmune complications. [1]

Rheumatoid arthritis, vitiligo, hemolytic anemia, thrombocytopenia, pyoderma gangrenosum, [2] and neutropenia have all been associated with CVID. [4]

Gastrointestinal diseases include pernicious anemia, a spruelike malabsorption disorder, autoimmune hepatitis, primary biliary cirrhosis, intestinal nodular lymphoid hyperplasia, atrophic gastritis, aphthous stomatitis, and inflammatory bowel disease. [31]

Malignancy

In patients with CVID, the risk of certain malignancies is high.

Lymphomas of a B-cell phenotype are of particular concern.

Malignancy is most likely associated with the Epstein-Barr virus.

The risk of gastric carcinoma is almost 50 times greater in patients with CVID than in other individuals.

Malignant melanomas are reported.

Dermatologic manifestations  [32]

Alopecia areata and alopecia universalis may occur. [33] Any time a person presents with recurrent infections and alopecia, CVID should be considered in the differential diagnosis. In one case study from the Hacettepe University in Turkey, Kiliç et al [34] reported a 12-year-old boy who had recurrent respiratory tract infections and chronic diarrhea since age 2 years. At age 2.5 years, he had a bandlike localized loss of hair (alopecia areata), and 1 year later, he had lost all body hair. His sister had similar findings and died from a pulmonary infection at the age of 7 years. On further studies, the patient was found to have decreased serum levels of IgG, IgA, and IgM and an increased number of CD8 cells. In addition, a skin biopsy specimen showed a perifollicular infiltrate of mononuclear cells.

Cutaneous infections may be serious too, with necrotizing fasciitis described in one patient. [35]

In patients with CVID, both non-necrotizing granulomas (sarcoidlike) and necrotizing granulomas (tuberculoid) have been observed. [5, 6, 8, 7]

In one case report by Pujol et al, [36] histopathologic biopsy showed perivascular lymphoid infiltrates in the upper and mid dermis, with central necrosis and a palisading granuloma.

A syndrome similar to sarcoidosis can affect patients with CVID. [10] This syndrome is characterized by noninfectious cutaneous granulomas, with underlying visceral granulomas of the lungs, liver, spleen, or conjunctiva in most patients. These cutaneous granulomas are nonspecific in patients with CVID and can appear as a maculopapular rash; as infiltrated erythematous papules, plaques, excoriated papules, and ulcers; or as nodules with ulcerations. On histologic analysis, such granulomas are noncaseating and involve the dermis or subcutaneous fat. These nonsarcoidal, nontuberculoid asymptomatic cutaneous granulomas often appear as multiple, nontender subcutaneous nodules, predominantly juxta-articular, and the skin overlying the nodules was either normal or slightly erythematous. [11]

Lesions frequently appear on the face and extremities and are always sterile. They often resolve with treatment of the underlying disease.

Residual hyperpigmentation may be observed.

The increased incidence of malignancy in patients with CVID is well known. In 1992, Green and Moschella [37] reported the first known case of a patient with CVID who developed multiple squamous cell carcinomas. Many other cases have been published since then. Patients with CVID have an increased risk for actinic keratosis and squamous cell carcinoma. This risk is not surprising given the increased incidence of skin cancer with prolonged iatrogenic immunosuppression, as in transplant recipients.

Other dermatologic manifestations of CVID include atopic dermatitis, cutaneous vasculitis including polyarteritis nodosa, [9] and polymorphic light eruption. [38] However, these are not specific markers of CVID, and they are not indications for a workup for CVID unless other implicating factors (eg, recurrent infections) are present.

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Complications

In any patient with a medical history of common variable immunodeficiency (CVID), the three following complications must be considered (see Physical):

  • Recurrent infections

  • Autoimmune phenomena

  • Malignancy

Death may result. A common cause of death in patients with CVID is lymphoma. Other causes include cor pulmonale secondary to chronic pulmonary infection, liver failure caused by viral or autoimmune hepatitis, malnutrition resulting from gastrointestinal tract disease, and other viral infections. Factors associated with mortality include low levels of IgG, poor T-cell responses to antigens, and a low percentage of peripheral B cells.

Other complications include chronic sinusitis, severe autoimmune thrombocytopenia, and hemolytic anemia.

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