This case study describes the diagnosis and treatment of a 7-month-old boy who came to Cincinnati Children’s Histiocytosis Center.

Clinical History

Starting at 2 months of age, the patient presented with rashes in his armpits, groin and scalp. He received multiple treatments for eczema with no response.

The patient also had recurrent ear drainage starting at 3 months of age. He received two sets of pressure equalization (PE) tubes to treat the drainage.

During surgery for a third set of PE tubes, the surgeon noticed a small mass next to the ear. The mass was biopsied and tested positive for Langerhans cell histiocytosis (LCH). The biopsy also revealed a BRAF-V600E gene mutation by immunohistochemistry (IHC) and polymerase chain reaction (PCR). Peripheral blood was also positive for BRAF-V600E.

Our Approach

We immediately began treatment with the oral MEK inhibitor trametinib. Although the patient tested positive for BRAF-V600E, we’ve found MEK inhibitors to be effective in treating LCH with any genetic mutation.

One week after starting the trametinib, the patient’s ear drainage stopped. The patient’s rashes began to subside two weeks after treatment. By six weeks, there was minimal evidence of the armpit rash.

Summary

After months of failed treatments, our patient’s symptoms began to subside just one week after starting trametinib. He experienced a full recovery and was able to avoid the side effects of systemic chemotherapy.

With these positive results, along with many others, Cincinnati Children’s is actively exploring clinical trials that use MEK inhibitors in the treatment of LCH and other histiocytic disorders. We hope that these trials will lead to a new standard therapy, with gene inhibitors becoming the universal frontline treatment for LCH and related conditions.

Thanks to gene inhibitors like trametinib, LCH is no longer a life-threatening disorder for infants and children.


Case Study: Diagnosis and Treatment of Infant with Systemic LCH

This case study describes the diagnosis and treatment of an infant who came to Cincinnati Children’s Histiocytosis Center. The young boy was born with a series of symptoms and complications related to LCH. 

Clinical History

Shortly after birth, the patient developed a rash covering his entire back. The patient also presented with a fever, reduced oral intake, diarrhea, vomiting, pancytopenia and hyperbilirubinemia. 

A skin biopsy tested positive for LCH. A subsequent PET scan also showed fluorodeoxyglucose (FDG) uptake throughout the patient’s skeleton and intestine, as well as patchy uptake in the liver. The PET scan also showed a lytic skull lesion. 

The biopsy revealed a BRAF-V600E gene mutation, and peripheral blood was also positive for BRAF-V600E.

Our Approach

We immediately began treatment with trametinib, an oral MEK inhibitor. We’ve found these inhibitors are effective in treating all LCH patients with gene mutations regardless of which mutation they have. 

Two weeks after starting the trametinib, the patient’s fever resolved, the vomiting and diarrhea stopped, and he began nursing and bottle feeding. The patient’s blood counts recovered and bilirubin levels declined.

By week six of trametinib treatment, the patient’s skin rash had resolved, and all the patient’s lab work returned normal results. The patient also started to gain weight. 

At 10 weeks, the patient’s PET scan looked completely normal. However, BRAF-V600E was still positive in the blood and bone marrow. 

Eight months later, he celebrated his first birthday. According to his pediatrician, he is a perfectly normal 1-year-old, with 18 teeth and a head full of hair. 

Summary

An infant born with systemic LCH and multiple life-threatening symptoms was able to make a full recovery into a happy, healthy baby. The patient was also able to avoid the severe side effects of systemic chemotherapy by undergoing a novel gene inhibitor treatment. 

Although the trametinib treatment saved the infant’s life, blood and bone marrow still tested positive for the BRAF-V600E mutation. More research is needed to determine the length of treatment needed to eliminate these mutations. To that end, we’re actively studying ways to monitor the clinical course of disease and better predict when mutant cells disappear from the body.

Cincinnati Children’s is also pursuing clinical trials for MEK inhibitors in hopes of making it the standard frontline treatment for LCH and histiocytosis patients with genetic mutations.