Prevention & Management of Infections
Prevention of Infections
Patients with Wiskott-Aldrich Syndrome are at high risk for infection with certain bacteria(capsulated bacteria) such as Hemophilus, Pneumococcus and Meningococcus. Vaccines can prevent some, but not all of the infections caused by these bacteria. Even after receiving a vaccine, patients with WAS may not produce an adequate antibody response to the vaccine. Antibody levels (titers) can be measured to check antibody responses and booster doses can be given if needed. Patients should receive the Hemophilus vaccine(HiB) and the pneumococcal conjugate vaccine(Prevnar) starting at the age of 2 months. At age two patients should receive the meningococcal conjugate vaccine (MCV4) and the pneumococcal polysaccharide vaccine (PPSV/pneumovax). A pneumovax booster is recommended 5 years after the first dose and is recommended every 5 years for patients who have undergone splenectomy. For further details, refer to the section on immunization.
Patients with WAS can get seriously ill from chicken pox and measles. Patients with severe eczema are at higher risk for serious complications. As they cannot receive vaccine to prevent the disease, it is important to receive prompt and appropriate care when they are exposed to chicken pox. Postexposure prophylaxis for chicken pox (varicella) is indicated. Varicella-zoster immune globulin/Varizig/IVIG is administered within 48 hours if possible, although it may be effective until 96 hours postexposure. After that time, acyclovir is recommended to prevent or lessen the disease severity beyond that time1, Please see the section on Exposure to Chicken Pox and Measles for details.
Patients with Wiskott-Aldrich Syndrome, particularly patients with Classic WAS are at a higher risk of serious infections with bacteria, viruses and fungi. Prophylactic medications to prevent these infections are to be determined on a case by case basis depending on the presence or absence of WASp, the number and severity of infections the patient has had, plans for transplant etc. Trimethoprim-Sulfamethoxazole (Bactrim, Septra) is recommended for prophylaxis of PCP2 (pneumocystis jirovecii) pneumonia as soon as the diagnosis of WAS is verified and continued until it is determined if the patient has XLT or Classic WAS. In patients with Classic WAS, prophylaxis is continued until the patient is transplanted. Studies show that prophylaxis with acyclovir is effective in the prevention of infection with herpes and is recommended for patients who are suspected of having Classic WAS, are WASp negative or are to undergo a HCT2. Infection with herpes complicates transplant and it is best to take measures to avoid it. Amphotericin B has not been shown to be of uniform benefit2 in the prevention of infection with fungi such as Apergillus and Candida. However, it's use can be considered as preventative therapy for patients who are WASp negative.
IVIG, every 3-4 weeks is recommended from the diagnosis of Classic WAS is made until the time that the patient is transplanted. Nowadays, most patients with Classic WAS are transplanted. In the rare event that a child with Classic WAS is not transplanted and does not receive Gene Therapy, then monthly IVIG should be continued. Prelimary results from a survey of patients with XLT has not shown that the routine use of routine IVIG in these patients does not seem to confer any survival benefit3.
Post Splenectomy Care
Patients with WAS who are splenectomized are at high risk for serious and life threatening infections. Postsplenectomy, prophylactic antibiotics are mandatory, although the patients who undergo splenectomy remain at considerable risk for overwhelming sepsis despite prophylaxis. Immunizations are mandatory with conjugated polysaccharide Hib and pneumococcal vaccines, influenza and with the meningococcal vaccines. Prophylaxis is to be continued even if the patient has a successful HCT because the incidence of sepsis continues to remain high4 even after successful HCT. Patients, especially those with WAS and those who have been splenectomized, should be closely monitored and infections aggressively treated with IV antibiotics and hospitalization as indicated. Any temperature over 38.3o C or 101o F should be considered as sepsis and treated as an emergency, cultures obtained and antibiotics started. See post splenectomy care for details.
IVIG after Splenectomy: Patients with Classic WAS should be on monthly IVIG whether they are splenectomized or not. There is no uniform consensus among experts regarding the use of IVIG in patients with XLT after splenectomy. Some experts feel that IVIG is useful in preventing infections from organisms such as drug resistant pneumococci and is therefore a useful adjunct to penicillin in the prevention of infection in these patients.
Management of Infections
Patients with Wiskott-Aldrich Syndrome should maintain a high degree of vigilance for infections, even while on antibiotics and having all immunizations. The risk of serious sepsis is high, particularly among patients who have been splenectomized. For management of post splenectomy patients please refer to the section on Prevention and Care of Bleeds. Fever is generally considered the hallmark of sepsis. it is important to know that these patients may be septic and not have a fever. Therefore if a patient is feeling unwell or uncomfortable, out of sorts, it is important to have them seen by a physician. Cultures should be obtained and antibiotics started immediately. Due to the risk of bleeding, intra muscular injection of antibiotics is generally avoided if possible. Whether patients need to be admitted to the hospital or need IVIG is determined on a case by case basis.
The most common infections are ear infections(otitis media), sinus infections and pneumonias, but infections can occur anywhere in the body. Infections should be addressed promptly with appropriate antibiotics and follow up to ensure complete resolution. Some patients may require hospitalization, IVIG and IV antibiotics. Sometimes prolonged or repeated courses of antibiotics may be required to clear infections completely.
School and Infection Control
Children with Wiskott-Aldrich Syndrome, particularly children with Classic WAS are more susceptible to infection, even with regular medical treatment and preventative medicines. If the child expresses any signs of illness or if the teacher notices that the child is ill, it should be brought to the nurses attention immediately. Depending on the circumstances, emergency care, including transport to an ER may be needed and parents must be contacted and informed. Outbreaks of communicable diseases in the school, particularly chicken pox, measles, mumps, mono, meningitis, influenza and hepatitis in the school should be reported to the parents at the earliest. Cuts and wounds should be cleaned and dressed, issues with bleeding addressed and parents should be notified.
Patients with Classic WAS can become seriously ill if they receive any live vaccine. If a particular vaccine is required by state law, parents can present documentation from the child's physician that he is exempt from that vaccine. Under no circumstances can a vaccine be given to a child without parental permission and parents should be notified of school wide immunizations. Patients with WAS are at risk of contracting infection from another individual who has received a live virus vaccine such as the chicken pox vaccine (varivax) or the intranasal flu vaccine (Flumist).
Infections with chicken pox can be serious and sometimes life threatening. Prompt medical attention should be given if chicken pox is suspected. Antiviral medications such as acyclovir or famcyclovir is indicated in these patients for chicken pox. Patients my have to be hospitalized for IV medications and IVIG may need to be given. A high degree of vigilance should be maintained until all the lesions resolve. Infections of the skin lesions with bacteria might occur and should be treated with the appropriate antibiotics right away. Any redness, swelling, continuing fevers, feeling of continuing discomfort etc should be attended to promptly. Patients with severe eczema are more prone to have complications from the chicken pox and extra care is needed. Routine care of chicken pox with oral antihistamines to control itching, oatmeal baths for comfort etc should be provided. Topical preparations that contain diphenhydramine (benadryl) should be avoided as it may cause an allergic reaction5.
Infection with herpes simplex (fever blister, cold sores) is not uncommon and can frequently recur during minor infections with the common cold, stress or fever or sun exposure. Sometimes recurrences can occur without a cause. Before the blisters appear the skin may feel itchy at the site, patients can experience a burning or tingling sensation. The sores most commonly affect the lips, mouth, nose, chin, or cheeks. Some patients do not have any discomfort and some patients find it very uncomfortable. Management of these infections is decided on a case by case basis in consultation with the physician. Sometimes, just topical antiseptic care may suffice. Infections can be treated with an antiviral medication such as acyclovir or famcyclovir. These medications generally shorten the duration of the symptoms. In older children and adults the formation of blisters can sometimes be avoided if acyclovir is started as soon as the tingling or burning sensation begin and the patient feels that another recurrence is about to begin. Topical acyclovir can be used on the blister6. While topical acyclovir does not cure the infection, it can help with the pain and discomfort and sometimes help heal the lesions faster. Cases of frequent recurrences may require prevention using oral antiviral medications everyday. If the cause of the flare ups is known, some recurrences may be preventable-such as, using a sunscreen in sun induced cases.
Secondary complications can occur. Superinfection of the blisters with bacteria can occur and can be treated with antibiotics. Children tend to itch or touch the blisters and then touch their eyes, spreading the infection to the eye. Infections of the eye can affect the cornea with serious consequences including blindness. It is important to monitor the lesions and prompt medical attention should be sought if there is suspicion of an eye infection. An ophthalmologist should be consulted and admission to the hospital for close monitoring and IV medication may be needed.
Warts and Molluscum Contagiosum: Patients with Wiskott-Aldrich Syndrome can have severe and recurrent bouts of warts and molluscum contagiosum. these are infections in the skin that are caused by viruses. In normal patients these infections disappear on their own. However, in patients with Wiskott-Aldrich Syndrome, they may cause widespread infections. They can be spread from one part of the body to another by picking at the lesions and touching normal skin. Early treatment can help reduce the spread of infections. Mayo clinic has an excellent section on the treatment of warts and what can be done to prevent them from spreading. Similarly there is an excellent section on the treatment of molluscum contagiosum and its prevention. Despite early and adequate treatment, mollusum infections can spread rapidly and in cases that are resistant to all of these conventional methods andtopical cidofovir may be helpful7.
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1. Prevention of Varicella; Recommendations of the Advisory Committee on Immunization Practices(ACIP) www.cdc.gov
2. Imai, K, Morio, T, Zhu, Y, Jin, Y, Itoh, S, Kajiwara, M, Yata, J, Mizutani, S, Ochs, HD and Nonoyama, S. Clinical course of patients with WASP gene mutations. Blood. 2004 Jan 15;103(2):456-64.
3. Albert, MH, Bittner, T, Stachel, D, Nonoyama, S, Notarangelo, L, Burns, S, Pellier, I, Strauss, G, Morio, T, Imai, K, Espanol, T, Gathmann, B, Hönig, M, Noordzij, JG, Nathrath, M, Meindl, A, Wintergerst, U, Fischer, A, Thrasher, A, Belohradsky, BH and Ochs, HD. Clinical Phenotype and Long Term Outcome in a Large Cohort of X-Linked Thrombocytopenia (XLT)/Mild Wiskott-Aldrich-Syndrome Patients. ASH Conference, Dec. 6-9 2008 http://www.hematology.org/meetings/2008/index.cfm
4. Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, Schulz A, Thrasher AJ, Mazzolari E, Slatter MA, Le Deist F, Blanche S, Veys P, Fasth A, Bredius R, Sedlacek P, Wulffraat N, Ortega J, Heilmann C, O'Meara A, Wachowiak J, Kalwak K, Matthes-Martin S, Gungor T, Ikinciogullari A, Landais P, Cant AJ, Friedrich W,
Fischer, A. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich Syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood. 2008 Jan 1;111(1):439-45.
5. Contact Dermatitis http://www.merck.com/
6. Acyclovir (Topical Route) http://www.mayoclinic.com/
7. Toro, JR, Wood, LV, Patel, NK, Turner, ML Arch Dermatol. 2000;136:983-985.