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August 24, 2023
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Children present differently with same complex condition

What’s your diagnosis?

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James Brien

Patient No. 1: A 3-month-old girl is diagnosed with severe thrush (Figure 1), resistant to treatment, along with persistent cutaneous rash, thought to be flaring episodes of candidiasis that never quite clear (Figure 2).

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Figure 1. White oral lesions resistant to treatment for thrush. Image: James H. Brien, DO.

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Figure 2. Persistent rash treated for candidiasis. Image: James H. Brien, DO.

She is admitted to the hospital due to respiratory distress with abnormal lungs on plane radiograph, which also revealed abnormal bone density of the mandible (Figure 3).

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Figure 3. Plain radiograph showing infiltrative lung disease and some missing mandibular bone density. Image: James H. Brien, DO.

Patient No. 2: A 12-month-old girl presents with a persistent bump on her forehead with an underlying lytic lesion (Figure 4), as well as a persistent rash and bilateral lesions in the molar part of her gingiva (Figure 5).

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Figure 4. Skull with small lytic lesion in frontal bone. Image: James H. Brien, DO.

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Figure 5. Gingival lesions. Image: James H. Brien, DO.

Patient No. 3 (courtesy of Maria H. Bernardo, MD): A 3-year-old boy with progressive distortion of his teeth (Figure 6) and pain in his right thigh (Figure 7).

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Figure 6. Gingival inflammation and distorted teeth with an alveolar mass. Image: Maria Bernardo, MD.

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Figure 7. MRI showing enhancement of proximal right femur. Image: Maria Bernardo, MD.

Patient No. 4: An otherwise healthy 6-year-old male with a painless, slow-growing bump on the top of his head (Figure 8), not associated with injury.

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Figure 8. Progressive painless swelling on top of the head. Image: James H. Brien, DO.

What’s your diagnosis?

A. Chronic mucocutaneous candidiasis

B. Incontinentia pigmenti

C. Langerhans cell histiocytosis

D. Osteosarcoma

Answer and discussion:

The patients in this vignette all have various manifestations of Langerhans cell histiocytosis (LCH), named after Paul Langerhans, a 19th century German pathologist. It is a complex spectrum of histiocytic infiltrative diseases that can involve any organ system. Eosinophilic granuloma is the mildest, benign form, shown in Figure 8, which was managed by surgical excision. Patient No. 1 had the more aggressive form, which was unresponsive to intensive therapy, succumbing to respiratory failure. The patients with the infiltrative lesions in the mouth and chronic skin rash have multisystem disease, but it is more manageable, usually with chemotherapy and/or radiation. Some patients may have endocrine disturbances, such as diabetes. With the variety of presentations, an infectious disease is often initially suspected. However, for any patient with chronic skin disease and bone loss or lesions, LCH should be considered early on.

While benign bone lesions are common in LCH, bone cancer is not (Figure 9), and it would not normally be accompanied with disease of the skin, mouth and other organ systems unless it was advanced.

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Figure 9. Osteosarcoma of distal femur with pathologic fracture. Image: James H. Brien, DO.

Chronic mucocutaneous candidiasis is a very rare genetic condition resulting in a T-lymphocyte-mediated immune disorder, the details of which are beyond the scope of this column. The disorder results in chronic but not invasive Candida infections involving skin and mucosa, and it may be associated with endocrine and other autoimmune disorders. Treatment depends on its severity, ranging from topical antifungals to systemic agents that are usually taken orally. If left untreated, it may result in the loss of nails and hair, and it could become a severe cosmetic problem (Figure 10). Inheritance may be autosomal dominant or recessive.

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Figure 10. Mucocutaneous candidiasis. Image: James W. Bass, MD.

Incontinentia pigmenti is an X-linked, genetic, multisystem disorder that is often fatal in males. It is usually first manifested as a skin disorder that progresses through three or possibly four stages. Initial skin lesions appear at or near the time of birth and may resemble cutaneous herpes. They frequently occur in streaks along the lines of Blaschko, in a linear pattern on the trunk and usually a whorl pattern on the head (Figure 11).

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Figure 11. Incontinentia pigmenti whorl pattern of rash on the scalp of a newborn. Image: James H. Brien, DO.

Subsequent stages involve linear blistering, then ultimately developing flat, brownish patches (Figure 12), as seen on the leg of the mother of the patient in Figure 11.

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Figure 12. Incontinentia pigmenti stage 3 pattern of rash on the leg of an adult woman — the mother of the patient shown in Figure 11. Image: James H. Brien, DO.

Columnist comments:

To read more about LCH, I would refer you to our column in the December 2019 issue a case presented by guest columnist Maria H. Bernardo, MD.

As the summer is coming to an end, children will be going back to the incubators we refer to as school classrooms. This is a good time to catch up on their immunizations, especially if new COVID-19 recommendations are made. Also, the AAP recently published guidance recommending the monoclonal antibody nirsevimab for all infants to prevent severe RSV. You can read more about the recommendation here. Lastly, do not forget about immunizing against influenza, especially your high-risk patients. An annual death rate in children in the United States due to influenza is usually between 100 and 200. Additionally, infected children become the source of adult cases, especially family members.

Please keep in touch.

For more information:

Brien is a member of the Healio Pediatrics Peer Perspective Board and an adjunct professor of pediatric infectious diseases at McLane Children's Hospital, Baylor Scott & White Health, in Temple, Texas. He can be reached at jhbrien@aol.com.