Question

As a pediatric immunologist, you have two patients both around a year old with similar but distinct symptoms. Both patients have hypothyroidism, and you have prescribed synthetic thyroid hormone to each. One patient, a girl aged 5 years, has had recurrent thrush infections (yeast infection of the mouth). And the other, a boy aged 18 months, has had several outbreaks of eczema. Family histories show male and female relatives with similar issues or worse for your female patient, and males relatives with similar issues for the male patient. You begin to suspect a heritable autoimmune disorder. (a) Which autoimmune disorders do you think each one has and why (at least 2 reasons for each) (abbreviations for diseases is ok). (b) What gene is defective in each disorder? And how would you test or confirm your diagnoses in part (a)? (c) Your partner suggests that both children should get bone marrow transplants. Do you agree? Why or why not in each case?

Answer 1

(1) The 5 years old female patient -

THYROID DISEASE

Candida (Yeast) Infections and Autoimmune Thyroid Disease

There is a potential link between thyroid disease and yeast infection.

Given that immune system malfunctioning is at the root of autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease, it's natural to wonder if it can also cause other issues in people with these conditions. Candidiasis—which can take several forms, including thrush and genital yeast infections—is one that has been discussed, given the important role your immune system plays in controlling growth of the fungus that's responsible for this problem.

In short, your autoimmune thyroid condition could influence your risk for yeast infections. But the connection is not all that clear or simple.

What Is Candida?

Candida (yeast) is a part of your normal flora that resides harmoniously with other organisms in your gut, reproductive tract, mouth, and skin. In people with healthy immune systems, the presence of Candida is harmless.   

Exploring the Candida and Thyroid Link

The scientific data supporting a link between Candida and autoimmune thyroid disease is overall scant. That said, if a link does exist, here are some potential theories:. Reason*******   

(a)Molecular Mimicry

Molecular mimicry implies there is a structural similarity between a foreign antigen (a substance that activates your immune system) and a host's self-antigen.

If molecular mimicry exists between Candida and the thyroid gland, a person's immune system may misguidedly launch an attack against their own thyroid—meaning the immune system mistakes the thyroid gland for a large yeast infection.

(b)Superantigen .   

Another theory that has been used to explain some infectious/autoimmune disease connections involves the concept of "superantigens."

A superantigen is a protein that triggers the mass activation of immune system cells. If overgrown Candida releases superantigens, the immune system may begin attacking the thyroid gland or other tissues within the body.

No Link at All

Of course, some experts believe that there is likely no link between Candida overgrowth and autoimmune thyroid disease.

Both Candida infections and autoimmune thyroid disease are fairly common diagnoses—so, it could just be coincidental that a person suffers from both.

Moreover, there are so many factors that contribute to Candida overgrowth besides an immune system problem—uncontrolled diabetes, obesity, poor hygiene, etc. Figuring out which factor is the main culprit behind a yeast infection can be tricky. In addition, there may be more than one factor involved. 18 months old male patient- Atopic dermatitis, or eczema, is a common skin disorder .virtually all of the studies that have defined the immune changes underlying eczema and are directing new treatment options have been done in adult skin. A study just published in the Journal of Allergy and Clinical Immunology characterizes immune changes for the first time in the skin of young children with eczemas Reason***"

some characteristics of eczema in children are the same as in adults, our study showed substantial differences that are important for understanding eczema in children and developing tailored treatments that maximize effectiveness and minimize potential side effects.

Currently, there are no targeted therapies for affected children, who are usually treated with topical steroids and, in severe disease, with immunosuppressant drugs. This new study evaluated both affected and unaffected skin in children within the first 6 months of their eczema, and compared the immune profiles to those in skin from healthy children and also to the affected and unaffected skin of adults with eczema.

The study verified the central and early role of the immune pathway that drives allergy (Th2), which helps explain the association of eczema, asthma, and allergies in kids. In a previous study, Paller and her associates found evidence of activation of this Th2 immune pathway in the blood as well. This pathway is currently the focus of development of targeted therapy for moderate-to-severe eczema, suggesting that these same agents being tested in adults could also be useful in young children. The observed increase in the biomarker for itch (IL-31) in skin points to another useful therapeutic target for children.

In studies of blood samples from children with and without eczema during the first years of the life, the eczema group showed suppressed development of an immune pathway that handles infections (Th1). This observation may help to explain why children with more severe eczema have more widespread infections of herpes and molluscum viruses.

Several differences in the skin of children with eczema raise doubts about findings in adults that are now considered central to understanding eczema. Adult eczema skin is deficient in the naturally produced agents that fight staph infections and certain viruses, and this deficiency has been thought to be an important reason for the high risk of these infections in eczema at all ages. But the levels of these antimicrobial factors in the skin of young children with eczema are very high, suggesting that deficiency does not play a role in the frequent skin infections at early ages.

A characteristic trait of eczema at any age is a poor skin barrier, which leads to dryness and easier entry of triggers of the immune system, such as bacteria, irritating substances and allergens. Filaggrin, a key protein in skin barrier function, is deficient in adults. This has been attributed to both genetic deficiency and immune cell products that prevent production of filaggrin. The deficit of filaggrin has been blamed for the poor skin barrier in eczema. In contrast to adults, however, the skin of young children with eczema was found to have plenty of filaggrin, despite its poor barrier function and skin thickening that is comparable to skin of adults with eczema. This unexpected finding suggests that the filaggrin deficit may not be the driving force for barrier issues and that treatments targeting this protein might not be as beneficial for children with eczema as for adults.

A panel of findings was generated from the blood and skin samples of each participating child affected by eczema. "Our study is the first step toward personalized medicine for children with eczema," says Paller. "We need to collect much more data to start matching targeted treatments to an individual's specific disease characteristics."

(2) gene responsible for autoimmune hypothyroidism-The cause of the most common type of congenital hypothyroidism, thyroid dysgenesis, is usually unknown. Studies suggest that 2 to 5 percent of cases are inherited. Two of the genes involved in this form of the condition are PAX8 and TSHR. These genes play roles in the proper growth and development of the thyroid gland. gene responsible for eczema-, atopic dermatitis is caused by inherited mutations in a single gene. One such gene is the CARD11 gene. The protein produced from this gene turns on signaling pathways involved in the development and function of immune system cells called lymphocytes. Diagnostic test****

Diagnosis

In general, your doctor may test for Hashimoto's disease if you're feeling increasingly tired or sluggish, have dry skin, constipation, and a hoarse voice, or have had previous thyroid problems or a goiter.

Diagnosis of Hashimoto's disease is based on your signs and symptoms and the results of blood tests that measure levels of thyroid hormone and thyroid-stimulating hormone (TSH) produced in the pituitary gland. These may including

A hormone test. Blood tests can determine the amount of hormones produced by your thyroid and pituitary glands. If your thyroid is underactive, the level of thyroid hormone is low. At the same time, the level of TSH is elevated because your pituitary gland tries to stimulate your thyroid gland to produce more thyroid hormone.

An antibody test. Because Hashimoto's disease is an autoimmune disorder, the cause involves production of abnormal antibodies. A blood test may confirm the presence of antibodies against thyroid peroxidase (TPO antibodies), an enzyme normally found in the thyroid gland that plays an important role in the production of thyroid hormones. But the TPO antibody test isn't positive in everyone with Hashimoto's thyroiditis. Many people have TPO antibodies present, but don't have a goiter, hypothyroidism or other problems.

In the past, doctors weren't able to detect an underactive thyroid (hypothyroidism), the main indicator of Hashimoto's disease, until symptoms were fairly advanced. But by using the sensitive TSH test, doctors can diagnose thyroid disorders much earlier, often before you experience symptoms.

Because the TSH test is the best screening test, your doctor will likely check TSH first and follow with a thyroid hormone test if needed. TSH tests also play an important role in managing hypothyroidism. These tests also help your doctor determine the right dosage of medication, both initially and over time. Diagnosis of eczema

No lab test is needed to identify atopic dermatitis (eczema). Your doctor will likely make a diagnosis by examining your skin and reviewing your medical history. He or she may also use patch testing or other tests to rule out other skin diseases or identify conditions that accompany your eczema. (3) There is no need for bone marrow transplant

Treatment for autoimmune hypothyroidism***

Treatment for Hashimoto's disease may include observation and use of medications. If there's no evidence of hormone deficiency, and your thyroid is functioning normally, your doctor may suggest a wait-and-see approach. If you need medication, chances are you'll need it for the rest of your life.

Synthetic hormones

If Hashimoto's disease causes thyroid hormone deficiency, you may need replacement therapy with thyroid hormone. This usually involves daily use of the synthetic thyroid hormone levothyroxine (Levoxyl, Synthroid, others).

Synthetic levothyroxine is identical to thyroxine, the natural version of this hormone made by your thyroid gland. The oral medication restores adequate hormone levels and reverses all the symptoms of hypothyroidism.

Monitoring the dosage

To determine the right dosage of levothyroxine initially, your doctor generally checks your level of TSH after six to eight weeks of treatment and again after any dose changes. Once the dose that normalizes your thyroid tests is determined, your doctor is likely to check your TSH level about every 12 months as the dosage you need may change. Excessive amounts of thyroid hormone can accelerate bone loss, which may make osteoporosis worse or add to your risk of this disease. Overtreatment with levothyroxine can also cause heart rhythm disorders (arrhythmias).

If you have coronary artery disease or severe hypothyroidism, your doctor may start treatment with a smaller amount of medication and gradually increase the dosage. Progressive hormone replacement allows your heart to adjust to the increase in metabolism.

Levothyroxine causes virtually no side effects when used in the appropriate dose and is relatively inexpensive. If you change brands, let your doctor know to ensure you're still receiving the right dosage.

Also, don't skip doses or stop taking the drug. If you do, signs and symptoms will gradually return. ****"Treatment of autoimmune eczema*** These treatments made with hydrocortisone steroids can quickly relieve itching and reduce inflammation. They come in different strengths, from mild over-the-counter (OTC) treatments to stronger prescription medicines. OTC hydrocortisone is often the first thing doctors recommend to treat mild eczema.