Immunisation in immunosuppressed dermatology patients

Immunodeficiency

Immunodeficiency is defined as inadequate functioning of the immune system. Immunodeficiency can be caused by inherited syndromes, infections, drugs, medical conditions, pregnancy, ageing and many other factors. It can occur at multiple points across the immune response. It can then lead to:

• Serious bacterial, fungal and viral infections
• Failure to thrive in infants and children
• Infections due to unusual or opportunistic organisms
• Delayed recovery from illness
• Non-infectious granulomatous skin disorders
• Certain cancers such as B-cell lymphoma and Kaposi sarcoma.

Immunodeficient people that become unwell should be carefully evaluated and infection should be treated aggressively.

Immunosuppression due to drugs

Immunosuppression is a general dampening of the immune response, usually in response to immunosuppressive drugs. The immune response is still mounted but it is not as efficient or efficacious.

Immunosuppressive drugs include:

• Systemic corticosteroids (for children, prednisone > 2mg/kg/day for 2 weeks or > 1mg/kg/day for > 4weeks)
• Methotrexate
• Ciclosporin
• Azathioprine
• Mycophenolate
• Cyclophosphamide
• Chemotherapy drugs
• Biologic agents

Lower doses or shorter courses of systemic steroids are not considered significantly immunosuppressive. Low-dose methotrexate used for skin diseases mainly acts as an anti-inflammatory drug and is only weakly immunosuppressive.

It is essential that people with immunodeficiency are adequately immunised against vaccine-preventable diseases.

Step 1: Take an immunisation history

Effective immunisation can be due to natural infection or vaccination. Prior to starting immunosuppressive therapy, determine the following:

• Prior vaccinations. Each country has its own recommendations for vaccinations with different vaccines given at different ages. Older people may not have received all the vaccines provided by the current schedule.
• History of varicella (chickenpox) and other vaccine-preventable diseases.
• Risk of tuberculosis (TB): for example, family history, travel to high-risk regions

The government-funded New Zealand National Immunisation Schedule (2018) includes the following vaccines:

• Diphtheria, whooping cough/pertussis, tetanus [DTaP] at 6 weeks, 3 months, 5 months, 4 years; and 11 years of age. Further diphtheria and tetanus is given during pregnancy and tetanus [Td] at 45 years and 65 years of age
• Polio [IPV]; at 6 weeks, 3 months, 5 months and 4 years of age
• Hepatitis B [HepB] at 6 weeks, 3 months and 5 months of age
• Pneumococcus [10-valent PCV] and Haemophilus [Hib] at 6 weeks, 3 months, 5 months and 15 months of age
• Rotavirus [RV1] at 6 weeks and 3 months
• Measles, mumps, rubella [MMR] at 15 months and 4 years
• Human papillomavirus (HPV9) at 11 or 12 years
• Varicella [VV] at 15 months
• Herpes zoster [HZV] at 65 years
• Influenza during pregnancy and annually from 65 years
• From time to time additional vaccines are included, such as prevalent meningococcus strains.

Vaccines recommended for travel may include hepatitis A, cholera and yellow fever (unfunded).

Live injected vaccines are MMR, oral polio (not IPV), varicella, zoster (shingles), yellow fever and BCG. There are live oral vaccines for rotavirus and typhoid and live nasal vaccine for influenza. These are best avoided while on immunosuppressive medication because they may result in severe vaccine reactions.

Step 2: Perform appropriate tests

If starting a cytotoxic drug such as cyclophosphamide or biologic therapy, or if considered at high-risk of TB from the history, screen for tuberculosis. Methods include:

• QuantiFERON Gold blood test
• Mantoux skin test
• Chest X-ray.

Check varicella, measles, hepatitis A/B/C and HIV serology. (There are no vaccines for hepatitis C or HIV).

Step 3: Vaccinate prior to starting immunosuppressive therapies

To avoid the risks of preventable infections:

• Give any outstanding vaccinations from the childhood schedule*. Note, the second MMR can be given as early as 1 month after the first.
• Immunise if not immune, even if previously vaccinated to the specific infection, including chickenpox/varicella-zoster vaccine.
• Recommend pneumococcal vaccine and the annual influenza vaccine. In New Zealand, the subsidy for pneumococcus and influenza vaccine is available for immunosuppressed patients under some circumstances.
• Recommend varicella and influenza vaccine to household contacts (‘ring-fencing’)
• Wait at least one month after live vaccination before commencing immunosuppression.

*New Zealand Immunisation Schedule 1 April 2018

Step 4: Vaccinations after starting immunosuppression

• Continue routine non-live vaccination schedule.
• Have seasonal influenza vaccine each autumn and consider a boost if immunosuppression is severe.
• Avoid live vaccination of patient and siblings once immunosuppressed (live polio, chickenpox/varicella, herpes zoster, yellow fever). MMR, BCG are exceptions and can still be given to immunosuppressed patients and their household contacts.

All patients on immunosuppressants should be warned that they are at risk of more severe infections than usual. They should be told to alert their care team if they are exposed to chickenpox (varicella) or measles.

Exposure of immunosuppressed patients to varicella and measles

Patients who are significantly immunosuppressed and are exposed to varicella or measles need to be given passive antibody protection, whether or not they have detectable antiviral IgG antibodies.

Passive antibody protection is not considered necessary for those who have evidence of immunity with detectable IgG antibodies and are taking methotrexate as their only immunosuppressive drug.

Varicella

There is a significant risk of varicella if a non-immune person is exposed to the virus during the infectious period. This occurs from 2 days before the rash appears until the blisters have crusted over. The incubation period after exposure is 7-21 days. ‘Significant’ exposure is considered to be 15 minutes of close contact/play with a contagious individual.

Chickenpox may also occur after direct contact with shingles/herpes zoster blisters.

If an immune-suppressed patient is in contact with varicella, passive protection should be provided with varicella-zoster immune globulin (VZIG) within 96 hours (ideally 72 hours) of contact.

Measles

There is a significant risk of measles if a non-immune person is exposed to the virus during the infectious period. This occurs from 5 days before the rash appears until 4 days after the onset of rash. The incubation period for measles is 10-14 days after exposure. ‘Significant’ exposure is considered to be 15 minutes of close contact/play with a contagious individual. Measles in the contact should be confirmed by viral serology, as measles rash may appear similar to other viral exanthems or morbilliform drug eruptions.

If an immune-suppressed patient is in contact with measles, the following treatment is recommended regardless of antibody status.

• Passive protection with normal immune globulin (NIG) or intravenous immunoglobulin within 6 days (ideally 72 hours) of contact
• MMR vaccination can be given within 72h to non-immunosuppressed with significant measles contact