Case 1
An 11-year-old girl with sickle cell trait and alpha thalassemia trait presented with dry, indurated, warm, erythematous patches on the left buttock and upper thigh that had been present for one month, and she was treated with oral antibiotics for presumed cellulitis. During the cephalexin course the skin became painful, and she developed daily, high fevers. Physical exam was notable for a well-appearing child with the affected areas weeping serosanguinous fluid. Laboratory data were significant for leukopenia with lymphopenia and neutropenia, anemia with reticulocytopenia, mildly elevated aspartate aminotransferase (AST), and elevated lactate dehydrogenase (LDH); inflammatory markers, uric acid, and peripheral blood smear were normal, the latter showing no evidence of blast cells or hemolysis (Table 1). While HLH was considered due to the continuous fever and cytopenias, there was no hepatosplenomegaly or other consistent laboratory abnormalities including hyperferritinemia, hypofibrinogenemia, or hypertriglyceridemia. Ultrasound of the lesion showed increased echogenicity of the subcutaneous fat, and magnetic resonance imaging (MRI) similarly showed findings suggestive of extensive soft tissue cellulitis with possible early myositis. Skin biopsy demonstrated a dense inflammatory infiltrate within the dermis and dermal-epidermal junction, consisting primarily of lymphocytes, macrophages, and plasma cells, without granulomas; the deep subcutaneous fat was not sampled. Wound culture was positive for Enterobacter cloacae and Methicillin Resistant Staphylococcus aureus, and after 1.5 weeks of ciprofloxacin treatment, her fever subsided. Due to the absence of expected systemic inflammation in the setting of infection, an extensive immunodeficiency evaluation was performed but was largely unrevealing for innate, humoral, and cellular defects. Though the patient remained afebrile for the next two months, her skin abnormalities persisted.
Over the following eight weeks, new non-tender, indurated nodules erupted on her arms and legs, followed by recurrence of fever and newly elevated inflammatory markers; erythrocyte sedimentation rate peaked at 57 mm/hr, though C-reactive protein remained normal. Additional laboratory data at this stage were significant for a low titer positive antinuclear antibody (ANA) 1:80 without specific antibodies to extractable nuclear antigens. Positron emission tomography with MR sequences showed non-specific abnormal fluorodeoxyglucose uptake at the areas of subcutaneous involvement and at scattered lymph nodes, but neither were concerning for neoplastic metabolic activity. Biopsy of a nodule showed histologic and immunohistochemical features of extensive lymphohistiocytic panniculitis. Among the infiltrate of mature CD4 + and CD8 + T-lymphocytes and CD163 + histiocytes surrounding fat lobules were atypical lymphocytes bearing larger, irregular nuclei, initially prompting concern for lymphoma (Fig. 1, 2). Also noted were more T-cells expressing TCR-γ than TCR-β. However, TCR-γ and TCR-β gene rearrangement studies did not demonstrate monoclonality, thereby essentially excluding SPTL and γδ-T-cell lymphoma, despite the atypical cellular appearance. Additionally, the low-titer ANA without other clinical features of SLE dramatically lowered suspicion for LP. CHP was considered the most rational diagnosis, so steroids and T-cell targeted therapy with tacrolimus, a calcineurin inhibitor, were initiated and titrated to a goal level of 5–10 mg/mL. The patient initially demonstrated a good response as the lesions decreased in size, the cytopenias improved, and she remained afebrile. In association with a discontinuation of therapy, the panniculitis lesions recurred, though without a robust rebound of the fever, cytopenias, or systemic inflammation.
Table 1
Laboratory data of Patient 1 and Patient 2.
Laboratory Test
|
Patient 1
|
Patient 2
|
WBC
|
2.3 K/𝜇L (4.3–11.4)
|
2.3 K/𝜇L (3.8–10.6)
|
ALC
|
0.9 K/𝜇L (1.2–4.3)
|
0.12 K/𝜇L (1.1-4.0)
|
ANC
|
1.1 K/𝜇L (1.6–7.9)
|
2.0 K/𝜇L (1.8–7.7)
|
Hemoglobin
|
10 g/dL (11.5–15.5)
|
8.8 g/dL (12.0–15.0)
|
Platelets
|
226 K/𝜇L (150.0-400.0)
|
121 K/𝜇L (150.0-450.0)
|
ESR
|
16 mm/hr (0–20.0)
|
Not available
|
CRP
|
< 0.5 mg/dL (0-0.9)
|
Not available
|
AST
|
70 U/L (10–40.0)
|
313 U/L (0–35.0)
|
ALT
|
20 U/L (10–35.0)
|
415 U/L (0–52.0)
|
Direct Bilirubin
|
0.2 mg/dL (0-0.3)
|
2.6 mg/dL (0-0.3)
|
Ferritin
|
144 ng/mL (10.0–82.0)
|
23,165 ng/mL (11–307.0)
|
Fibrinogen
|
257 mg/dL (172.0-471.0)
|
62 mg/dL (200–450.0)
|
PT
|
Not available
|
16.9 sec (12.1–14.5)
|
PTT
|
Not available
|
32 sec (22.0–36.0)
|
Triglycerides
|
70 mg/dL (28.0-129.0)
|
472 mg/dL (40.0-200.0)
|
LDH
|
1,231 U/L (380.0-770.0)
|
1,530 U/L (0-250.0)
|
Uric acid
|
3.5 mg/dL (3.0-4.7)
|
4.2 mg/dL (1.5–6.5)
|
WBC, white blood cell count; ALC, absolute lymphocyte count; ANC, absolute neutrophil count; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; AST, aspartate aminotransferase; ALT, alanine transaminase; PT, prothrombin time; PTT, partial thromboplastin time; LDH, lactate dehydrogenase