What's Your Diagnosis?

A 3-year-old male develops foot pain, gingival edema

A 3-year-old male living in Puerto Rico presented with progressive bilateral foot and lower extremity pain. He had been healthy until 4 months earlier, when he was diagnosed with influenza B. In addition to the common symptoms of influenza at that time, he also had the onset of pain in both feet. This pain continued, with a pattern of getting worse in the mornings, and reached a point where the patient refused to wear shoes. An orthopedic consultant failed to find a problem, and the patient was treated with pain medication, which had minimal effect. As his pain continued, he began having painful gingival swelling and erythema. His dentist referred him to a local hospital, where he was diagnosed with gingivitis and myositis, supported by an elevated CPK of 1760 and an ESR of 40, with a negative bone scan. The patient’s gingival edema worsened, with friable bleeding gums and ongoing leg pains, and he was taken to the regional medical center. Additional history revealed that he never had fever, night sweats or joint inflammation or swelling, but he did have a mild, transient rash, now resolved.

James H. Brien

His past medical history is that of a previously healthy, unvaccinated 3-year old male, with no travel history or exposure to sick contacts or unusual animal or insect exposure. His dietary history is described as being a “picky eater.”

Maria H. Bernardo

Examination on admission revealed normal vital signs and weight. The only positive findings included refusal to bear weight and mouth findings of inflamed gingival hyperplasia, with left maxillary and mandibular alveolar masses, which were very friable and bled easily when manipulated (Figure 1).

Figure 1. Bleeding and swollen gingiva with alveolar mass.

Source: Maria H. Bernardo, MD

His admitting lab results revealed a normal CBC, CRP, aldolase, CPK (which had been elevated), CMP, hepatitis profile, parvovirus, EBV, rubella, C3, C4, CH50, D-dimers, PT, PTT, EBV and CMV IgM, and blood cultures were negative. However, the ESR was 51 and a vitamin C level was 0. Imaging studies included normal CT scans of the head, chest, abdomen and negative brain MRI. A repeat bone scan showed uptake in the right proximal femur, with a follow up MRI of lower extremities revealing increased signal as well (Figure 2), along with bilateral myositis, infiltrative bone lesions and periosteal elevation. He had two bone marrow aspirations with negative results, but the oncologists noted soft bone when inserting the needle.

Figure 2. MRI showing enhancement of proximal right femur.

Source: Maria H. Bernardo, MD

Empiric therapy was started with cefepime and clindamycin pending a diagnosis. A biopsy of the mouth lesions revealed the final diagnosis.

What’s your diagnosis?

  • A. Multifocal osteomyelitis
  • B. Langerhans cell histiocytosis
  • C. Osteosarcoma
  • D. Scurvy

Case Discussion

The best answer is B, Langerhans cell histiocytosis (LCH), although it was likely complicated by vitamin C deficiency. The biopsy was positive for langerin, a protein present in Langerhans cells and consistent with LCH. The genetics and biochemistry are beyond the scope of this column (which is code for beyond my ability to understand and condense it into this format). For those who want to see more pictures and discussion about LCH, I would refer you to my column in the August 2010 issue. In that column, I noted that this is an uncommon condition, formerly referred to as histiocytosis X, which included three types: (1) Letterer-Siwe disease, (2) Hand-Schüller-Christian disease and (3) eosinophilic granuloma. That classification faded into history, as frequent overlap of features led to the thought that these represent a spectrum of the same disease. However, now the disease is considered a rare type of cancer by the NIH. In addition to bone involvement, this disease can involve multiple organs, including lungs, liver, spleen and skin.

The treatment of this condition is usually best managed by an oncologist, as the treatment is similar to that of some cancers. The prognosis for the most severe type of LCH is guarded, with only about 80% surviving, according to St. Jude Children’s Research Hospital. For a brief but excellent review, I would recommend referring to the National Cancer Institute at the NIH online.

Figure 3. Multifocal osteomyelitis.

Source: James H. Brien, DO

Multifocal osteomyelitis usually presents as untreated acute hematogenous osteomyelitis, with spread via the circulation, or by direct spread, or both. An example of multifocal osteomyelitis of the left femur and tibia is shown in Figure 3 in the same patient — a child with MSSA sepsis, osteomyelitis of the femur and proximal tibia and a septic hip, 1 week after the onset of fever and pain. One would expect fever and multiple lab and imaging abnormalities with this condition.

Osteosarcoma may present with a pathologic fracture and a bone mass (Figure 4), with the distal femur being the most common site. It would not be associated with the mouth findings of this case.

Figure 4. Osteosarcoma of distal femur with pathologic fracture.

Source: James H. Brien, DO

The origin of the word “scurvy” is a bit unclear but dates back to the mid-16th century with French and Dutch origins, meaning “covered with scabs.” However, the description of the disease dates back to Hippocrates. Depending on the severity and duration (usually over 1 month) of the deficiency, there are numerous findings that can develop due to a lack of vitamin C in the diet. Of the classic findings of scurvy, swollen and bleeding gingiva with tooth loss and sore legs and arms may appear early. The transient rash described in this patient may have also been due to evolving scurvy. The patient had no other apparent signs of scurvy (hair and nail changes, easy bruising, arthropathy and anemia). This patient certainly had the mouth findings, but the alveolar mass that was biopsied would not be an expected finding. Therefore, this patient had a very uncommon disease (LCH) in the face of an uncommon vitamin C deficiency. He may have had elements of both, but LCH best explains the physical and imaging findings.

Columnist comments: I want to thank Dr. Maria Bernardo for contributing this very interesting case. This is her second case to appear in this column. The first was a very unusual infection of the hand in November 2011.

Disclosures: Bernardo and Brien report no relevant financial disclosures.

A 3-year-old male living in Puerto Rico presented with progressive bilateral foot and lower extremity pain. He had been healthy until 4 months earlier, when he was diagnosed with influenza B. In addition to the common symptoms of influenza at that time, he also had the onset of pain in both feet. This pain continued, with a pattern of getting worse in the mornings, and reached a point where the patient refused to wear shoes. An orthopedic consultant failed to find a problem, and the patient was treated with pain medication, which had minimal effect. As his pain continued, he began having painful gingival swelling and erythema. His dentist referred him to a local hospital, where he was diagnosed with gingivitis and myositis, supported by an elevated CPK of 1760 and an ESR of 40, with a negative bone scan. The patient’s gingival edema worsened, with friable bleeding gums and ongoing leg pains, and he was taken to the regional medical center. Additional history revealed that he never had fever, night sweats or joint inflammation or swelling, but he did have a mild, transient rash, now resolved.

James H. Brien

His past medical history is that of a previously healthy, unvaccinated 3-year old male, with no travel history or exposure to sick contacts or unusual animal or insect exposure. His dietary history is described as being a “picky eater.”

Maria H. Bernardo

Examination on admission revealed normal vital signs and weight. The only positive findings included refusal to bear weight and mouth findings of inflamed gingival hyperplasia, with left maxillary and mandibular alveolar masses, which were very friable and bled easily when manipulated (Figure 1).

Figure 1. Bleeding and swollen gingiva with alveolar mass.

Source: Maria H. Bernardo, MD

His admitting lab results revealed a normal CBC, CRP, aldolase, CPK (which had been elevated), CMP, hepatitis profile, parvovirus, EBV, rubella, C3, C4, CH50, D-dimers, PT, PTT, EBV and CMV IgM, and blood cultures were negative. However, the ESR was 51 and a vitamin C level was 0. Imaging studies included normal CT scans of the head, chest, abdomen and negative brain MRI. A repeat bone scan showed uptake in the right proximal femur, with a follow up MRI of lower extremities revealing increased signal as well (Figure 2), along with bilateral myositis, infiltrative bone lesions and periosteal elevation. He had two bone marrow aspirations with negative results, but the oncologists noted soft bone when inserting the needle.

Figure 2. MRI showing enhancement of proximal right femur.

Source: Maria H. Bernardo, MD

Empiric therapy was started with cefepime and clindamycin pending a diagnosis. A biopsy of the mouth lesions revealed the final diagnosis.

What’s your diagnosis?

  • A. Multifocal osteomyelitis
  • B. Langerhans cell histiocytosis
  • C. Osteosarcoma
  • D. Scurvy
PAGE BREAK

Case Discussion

The best answer is B, Langerhans cell histiocytosis (LCH), although it was likely complicated by vitamin C deficiency. The biopsy was positive for langerin, a protein present in Langerhans cells and consistent with LCH. The genetics and biochemistry are beyond the scope of this column (which is code for beyond my ability to understand and condense it into this format). For those who want to see more pictures and discussion about LCH, I would refer you to my column in the August 2010 issue. In that column, I noted that this is an uncommon condition, formerly referred to as histiocytosis X, which included three types: (1) Letterer-Siwe disease, (2) Hand-Schüller-Christian disease and (3) eosinophilic granuloma. That classification faded into history, as frequent overlap of features led to the thought that these represent a spectrum of the same disease. However, now the disease is considered a rare type of cancer by the NIH. In addition to bone involvement, this disease can involve multiple organs, including lungs, liver, spleen and skin.

The treatment of this condition is usually best managed by an oncologist, as the treatment is similar to that of some cancers. The prognosis for the most severe type of LCH is guarded, with only about 80% surviving, according to St. Jude Children’s Research Hospital. For a brief but excellent review, I would recommend referring to the National Cancer Institute at the NIH online.

Figure 3. Multifocal osteomyelitis.

Source: James H. Brien, DO

Multifocal osteomyelitis usually presents as untreated acute hematogenous osteomyelitis, with spread via the circulation, or by direct spread, or both. An example of multifocal osteomyelitis of the left femur and tibia is shown in Figure 3 in the same patient — a child with MSSA sepsis, osteomyelitis of the femur and proximal tibia and a septic hip, 1 week after the onset of fever and pain. One would expect fever and multiple lab and imaging abnormalities with this condition.

Osteosarcoma may present with a pathologic fracture and a bone mass (Figure 4), with the distal femur being the most common site. It would not be associated with the mouth findings of this case.

PAGE BREAK
Figure 4. Osteosarcoma of distal femur with pathologic fracture.

Source: James H. Brien, DO

The origin of the word “scurvy” is a bit unclear but dates back to the mid-16th century with French and Dutch origins, meaning “covered with scabs.” However, the description of the disease dates back to Hippocrates. Depending on the severity and duration (usually over 1 month) of the deficiency, there are numerous findings that can develop due to a lack of vitamin C in the diet. Of the classic findings of scurvy, swollen and bleeding gingiva with tooth loss and sore legs and arms may appear early. The transient rash described in this patient may have also been due to evolving scurvy. The patient had no other apparent signs of scurvy (hair and nail changes, easy bruising, arthropathy and anemia). This patient certainly had the mouth findings, but the alveolar mass that was biopsied would not be an expected finding. Therefore, this patient had a very uncommon disease (LCH) in the face of an uncommon vitamin C deficiency. He may have had elements of both, but LCH best explains the physical and imaging findings.

Columnist comments: I want to thank Dr. Maria Bernardo for contributing this very interesting case. This is her second case to appear in this column. The first was a very unusual infection of the hand in November 2011.

Disclosures: Bernardo and Brien report no relevant financial disclosures.