Understanding Your Child’s Condition & Diagnosis

Histiocytosis is a group of diseases that are not necessarily cancer but involve abnormal growth of cells which are part of immune system, most notably histiocytes (a form of white blood cell). These diseases can occur anywhere in body, but are most notably found in the skin and bone. Histiocyte disorders are varied and rare, and while they can be found in adults, they are most often found in children 10 and under. The most common disorder is Langerhans Cell Histiocytosis (LCH) followed by Hemophagocytic Lymphohistiocytosis (HLH). There are even more rare Histiocyte disorders, and we treat them all at Phoenix Children’s Hospital.

Patients with Langerhans Cell Histiocytosis (LCH)

Langerhans Cell Histiocytosis (LCH) is the most common type of Histiocytosis, affecting 1 in 200,000 people, but it is still considered a rare disease involving the histiocyte. The job of the histiocyte is to help destroy certain foreign materials and fight infection, but for unknown reasons, patients with this disease have too many histiocytes (Langerhans cells).  These cells accumulate in different organs and can result in a variety of symptoms.

LCH has also been known as Histiocytosis-X, Eosinophilic Granuloma, Letterer-Siwe disease, and Hand-Schuller-Christian Syndrome.

There are a number of other terms that have been used to describe syndromes that are considered to be LCH. These include: Reticuloendotheliosis, Hasimoto-Pritzker syndrome, Self-healing histiocytosis, Pure cutaneous histiocytosis, Langerhans cell granulomatosis, Type II histiocytosis, and Non-lipid reticuloendotheliosis.

The cause of LCH is unknown. It may be triggered by an unusual reaction of the immune system from something commonly found in the environment, and it is not known to be hereditary or communicable.

Over the years, cancer treatments have been used in patients with Histiocytosis. Consequently, hematologists and oncologists, who treat cancer, also treat children with LCH.  However, the disease is not cancer. Chemotherapy, if used, is given in much lower doses than that which cancer patients receive.

The vast majority of patients will survive the disease. Some may develop life-long chronic problems, while others remain symptom free. In some cases the disease is fatal. Usually these are very young infants who have a rapid downhill course and do not respond to any known treatment. Whether or not the disease responds to treatment will often depend on the extent of organ involvement; however, it is often difficult to make definite predictions. Our physicians will be able to discuss your child’s likelihood of responding to treatment.

LCH Symptoms:

Histiocytosis varies greatly from patient to patient, and you child may not experience any or all of these symptoms.

  • Skin: Scaly, waxy rash that does not respond to treatment.
  • Bone: Single or multiple lesions, bone pain, headaches (skull lesions), and limp (leg lesions).
  • Gastrointestinal: Abdominal pain and jaundice, vomiting, diarrhea, bleeding from the esophagus, and weight loss.
  • Pituitary Gland (known as Diabetes Insipidus): Dehydration, polydipsia (excessive thirst), polyuria (excessive urination), short stature, and delayed puberty.
  • Pulmonary: Feeding problems (infants), vomiting, diarrhea, chest pain, labored breathing, failure to thrive, cough, coughing blood, and weight loss.
  • Brain: Mental deterioration, diabetes insipidus, headaches, dizziness, seizures, abnormal protrusion of eyeballs, difficulty swallowing, and vomiting.
  • Mouth: Pain and swelling of face, loosening and loss of teeth, swollen gums with hemorrhage, and swollen lymph nodes in neck.
  • Ear: Inflamed condition of ear canal, rash behind ear or on scalp, formation of cysts in the ear, and oozing from ear (foul-smelling discharge).
  • Organ: Lung, liver, or spleen dysfunction.
  • Eye: Vision problems or eye bulging.

Learn More About LCH.

Patients with Hemophagocytic Lymphohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of the immune system primarily affecting young infants and children. The prevalence of HLH is 1.2 in every 1,000,000 children under the age of 15.

The disease usually presents with fever and sometimes other symptoms of an infection. In many cases, a pathogen (viral, bacterial, etc.) can be identified. The human body contains many cells including T-cells and histiocytes that fight infection. The activation of these cells causes an inflammatory reaction in the body.  Normally, when the pathogen has been eliminated, the inflammatory reaction is turned off and the immune system returns to its steady state. In HLH patients, due to defect of the immune system, the inflammatory reaction persists and causes the symptoms of HLH.

We currently know that HLH occurs either on the basis of a genetic defect or as a secondary form with underlying diseases such as infections, cancer, or rheumatic diseases. In the primary form, also known as Familial Hemophagocytic Lymphohistiocytosis (FHL or FHLH), defective genes are inherited from both the mother and the father (autosomal recessive inheritance). FHL is diagnosed if there is more than one affected child in the family and/or a gene defect has been determined. FHL should be suspected if the symptoms do not disappear with treatment or if symptoms recur when therapy has been stopped. The onset of FHL is usually early in life, and a persistent cure can only be achieved with bone marrow transplantation (BMT). It is important to know that infections can trigger both the familial and the secondary disease.

So far, 3 gene defects have been identified, which account for approximately fifty to eighty percent of the familial cases, depending on the population that has been analyzed. Two of the genes, PRF1 and UNC13D, are responsible for the synthesis of proteins, perforin, and MUNC13-4 that are involved in the killing process of infectious pathogens. They are believed to also have a function in switching off immune responses. The precise mechanism, however, is not fully understood. A third defect affecting the Syntaxin 11 (STX11) gene has so far only been detected in patients of Turkish origin. The function of the mutated protein remains to be elucidated. There remains a considerable percentage of FHL patients with no known underlying gene defect.

In cases of secondary HLH, a condition of temporary immunodeficiency seems to contribute to the development of the disease.

HLH Symptoms:

Typical symptoms of HLH besides persistent fever are

  • Pallor (paleness)
  • Jaundice
  • Liver and spleen enlargement
  • Neurological symptoms, such as irritability or even seizure
  • Severe decline of the blood cell counts (red and white blood cells and platelets)

Because symptoms can vary widely, it is sometimes difficult for the physician to make a diagnosis of HLH early in the course of the disease without the help of specialized laboratory tests.

Learn More About Other Histiocyte Disorders

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