CLINICAL CASE PORTO, 25 FEBRUARY 2014 EVA PADRÃO, VANESSA SANTOS, PATRÍCIA CAETANO MOTA, NATÁLIA MELO, CONCEIÇÃO SOUTO MOURA, SUSANA GUIMARÃES, JOSÉ PEREIRA, RUI CUNHA, ANTÓNIO MORAIS PORTO, 25 FEBRUARY 2014

identification JFSM Male gender 63 years-old Caucasian Resident in Maia Retired (occupation: glass fitter)

Past medical history Hypertension Dyslipidemia Esophageal hiatus hernia Surgery to left knee bursitis in 2010 Smoker (25 pack-years) Allergy to ibuprofen; no other allergies documented No drugs or alcohol consume; no sexual risk behaviours; no recent traveling abroad

usual medication Losartan/hydrochlorothiazide 50/12.5 mg id Fenofibrate 200 mg id Note: Fenofibrate (initiated in September 2013) was suspended by patient initiative for some time due to development of skin reaction Meanwhile, administration was resumed two weeks before seeking medical assistance

Main complaints Fever Myalgia maculopapular rash

History of present illness At the beginning of October 2013 fever, myalgia and sweating medicated with amoxicillin/clavulanic acid and, subsequently, levofloxacin 2 weeks later maintenance of complaints + appearance of skin rash on the trunk and limbs hospitalized for monitoring and antibiotic treatment (usual medication stopped during this period) discharged 8 days later with a diagnosis of community-acquired pneumonia

History of present illness Chest X-ray by the time of admission, with left perihilar opacity and a micronodular pattern at the right lung base.

History of present illness 3 days after discharge re-initiates fever, myalgia and pruriginous rash on inner thighs  hospitalized usual medication was resumed

physical examination Oximetry (FiO2 21%): 98% No signs of respiratory distress Pulmonary auscultation: bilateral symmetric sounds with crackles in both lung bases Maculopapular skin lesions on the trunk and limbs, most evident in the inner thighs and abdominal wall with dermographism No other changes

Diagnostic test results Blood analysis: Normal hemoglobin Mild leukocytosis [12.33x109/L (N 4-11x109/L)], with eosinophilia [18.2% – 2.24x109/L (N 0.6-4.6%)] CRP 132.9 mg/L

Diagnostic test results Chest X-ray: heterogeneous left perihilar opacity and a micronodular pattern at the right lung base

Diagnostic test results High-resolution Chest CT: peribronchovascular opacity most evident in the periphery of the LLL, associated with air bronchogram and slight thickening of the interlobular septa; bilateral discrete ground-glass micronodular pattern

Diagnostic test results High-resolution Chest CT: peribronchovascular opacity most evident in the periphery of the LLL, associated with air bronchogram and slight thickening of the interlobular septa; bilateral discrete ground-glass micronodular pattern

Diagnostic test results Bronchoscopy: without morphological or topographical features BAL: lymphocyte 6.4%, macrophages 83.8%, neutrophils 0.4%, eosinophils 9%, mast cells 0.4%; cytology negative for malignant cells, no microorganisms were found

Diagnostic test results Transthoracic needle aspiration biopsy

Two adequate fragments of transthoracic biopsy

Expansion of alveolar septa by edema and a mixed inflammatory infiltrate Organizing pneumonia lesions and pneumocyte hyperplasia

Prominent eosinophilic interstitial infiltrate, with some clustering; few within alvelar spaces

Diagnosis: Morphologic features of eosinophilic pneumonia (integrate in the clinical/radiologic context)

Diagnostic test results Complementary blood analysis IgE 737 kU/L (N < 114) Sedimentation velocity 48 mm/1st h (N < 20) Remaining immunological, autoimmune and serological study without abnormalities Immunophenotyping of peripheral blood: T cells with abnormal expression of CD3; polyclonal B population Bone marrow biopsy: reactive changes Skin biopsy: chronic nonspecific epidermotropic dermatitis Cultural tests (hemocultures, urine culture, stool examination, BAL, pulmonary biopsy): negative

Temporal relation with fenofibrate introdution SUMMARY FEVER SKIN RASH EOSINOPHYLIA PULMONARY OPACTITIES Temporal relation with fenofibrate introdution

Final diagnosis PROBABLE DRESS SYNDROME (associated with fenofibrate) EOSINOPHILIC PNEUMONIA (in the context of fenofibrate?)

evolution Fenofibrate was stopped Subsequently resolution of symptoms O doente só fez antiboterapia e parou fibrato. Não fez corticoterapia! Marked regression of parenchymal consolidation areas, persisting mild residual features.

DISCONTINUATION OF FIBRATE

T cells with abnormal expression of CD3 evolution February 2014 Clinical, radiological and analytical improvement BLOOD ANALYSIS OCTOBER 2013 FEBRUARY 2014 Normal Values Hemoglobin 13.2 g/dL 15 g/dL 13-18 Leucocytes 12.33x109/L 6.88x109/L 4-11x109/L Eosinophils 2.24x109/L (18.2%) 0.38x109/L (5,5%) 0.4-4.6% Sedimentation velocity 48 mm/1st h 6 mm/1st h 0-20 CRP 132.9 mg/L 2.4 mg/L < 3 IgE 737 kU/L 149 kU/L < 114 Immunophenotyping T cells with abnormal expression of CD3 Normal