Baseline clinical evaluation recommendations for patients with RDD
| Recommendation . |
|---|
| Medical history |
| Constitutional: fevers, night sweats, fatigue |
| HEENT: cervical swelling, double vision, retroorbital pain, eyelids/lacrimal swelling, nasal obstruction, epistaxis, hyposmia, oral sores, or pain |
| Cardiovascular: dyspnea, orthopnea |
| Pulmonary: dyspnea, cough |
| GI: abdominal pain, constipation, hematochezia |
| Renal: hematuria, flank pain |
| Musculoskeletal: bone pain |
| Dermatologic: rash, pruritus |
| Endocrine: polydipsia/polyuria |
| Neurologic: headaches, seizures, gait difficulty, limb or facial weakness, sensory changes, hearing impairment, new or focal back pain |
| History of: autoimmune disease, ALPS, malignancy, LCH, or another histiocytic disorder |
| Family history (pediatric patients): consanguineous parents, autoimmune disease, Turkish/Pakistani or Middle Eastern background |
| Physical examination |
| HEENT: dysmorphic face and hearing abnormalities (familial RDD), enlarged cervical nodes, proptosis, lesions of oral mucosa, enlarged tongue or tonsils |
| Cardiac: hypertension, irregular pulse, cardiomegaly, murmurs |
| Thoracic: diminished lung aeration, rales, axillary nodes, breast mass |
| Skin: nodules, papules, or plaques |
| Abdominal: flank mass, hepatosplenomegaly, enlarged inguinal nodes |
| Genital: testicular mass or enlargement |
| Musculoskeletal: osseous mass |
| Neurologic: disconjugate gaze, cranial nerve palsies, dysarthria, ataxic gait, hemiparesis, hyperreflexia |
| Radiological evaluation |
| All patients |
| PET/CT: recommended by some authors for all patients, including children (judicious use is recommended in this age group), but no universal consensus was reached |
| Ultrasound neck/abdomen, chest X-ray or whole-body MRI: reasonable alternatives |
| Selected patients based on symptoms or organ involvement |
| CT sinuses with contrast |
| MRI orbit/brain with contrast |
| MRI spine with contrast |
| High-resolution CT chest |
| Pulmonary function tests |
| Thyroid ultrasound |
| Testicular ultrasound |
| Laboratory evaluation |
| Complete blood count with differential |
| Serum immunoglobulins |
| ALPS panel, ANA, RF, HLA-B27: if autoimmune disease is suspected |
| Erythrocyte sedimentation rate |
| Complete metabolic panel, coagulation parameters, uric acid, LDH |
| Patients with anemia: Coombs test, haptoglobin, reticulocyte count and blood smear |
| Targeted-capture, next-generation sequencing of lesional tissue for mutations in RAF-RAS-MEK-ERK pathway (eg, KRAS, MAP2K1): in severe or refractory cases |
| Bone marrow aspirate/biopsy (if cytopenias or abnormal peripheral blood smear are present) |
| Lumbar puncture (for brain lesions inaccessible to biopsy); CSF pleocytosis with emperipolesis visible upon cytologic examination is indicative of RDD |
| Check lesional tissue for PDGFR-α/β and c-kit |
| Germ line mutations in SLC29A3: if familial RDD is suspected |
| Recommendation . |
|---|
| Medical history |
| Constitutional: fevers, night sweats, fatigue |
| HEENT: cervical swelling, double vision, retroorbital pain, eyelids/lacrimal swelling, nasal obstruction, epistaxis, hyposmia, oral sores, or pain |
| Cardiovascular: dyspnea, orthopnea |
| Pulmonary: dyspnea, cough |
| GI: abdominal pain, constipation, hematochezia |
| Renal: hematuria, flank pain |
| Musculoskeletal: bone pain |
| Dermatologic: rash, pruritus |
| Endocrine: polydipsia/polyuria |
| Neurologic: headaches, seizures, gait difficulty, limb or facial weakness, sensory changes, hearing impairment, new or focal back pain |
| History of: autoimmune disease, ALPS, malignancy, LCH, or another histiocytic disorder |
| Family history (pediatric patients): consanguineous parents, autoimmune disease, Turkish/Pakistani or Middle Eastern background |
| Physical examination |
| HEENT: dysmorphic face and hearing abnormalities (familial RDD), enlarged cervical nodes, proptosis, lesions of oral mucosa, enlarged tongue or tonsils |
| Cardiac: hypertension, irregular pulse, cardiomegaly, murmurs |
| Thoracic: diminished lung aeration, rales, axillary nodes, breast mass |
| Skin: nodules, papules, or plaques |
| Abdominal: flank mass, hepatosplenomegaly, enlarged inguinal nodes |
| Genital: testicular mass or enlargement |
| Musculoskeletal: osseous mass |
| Neurologic: disconjugate gaze, cranial nerve palsies, dysarthria, ataxic gait, hemiparesis, hyperreflexia |
| Radiological evaluation |
| All patients |
| PET/CT: recommended by some authors for all patients, including children (judicious use is recommended in this age group), but no universal consensus was reached |
| Ultrasound neck/abdomen, chest X-ray or whole-body MRI: reasonable alternatives |
| Selected patients based on symptoms or organ involvement |
| CT sinuses with contrast |
| MRI orbit/brain with contrast |
| MRI spine with contrast |
| High-resolution CT chest |
| Pulmonary function tests |
| Thyroid ultrasound |
| Testicular ultrasound |
| Laboratory evaluation |
| Complete blood count with differential |
| Serum immunoglobulins |
| ALPS panel, ANA, RF, HLA-B27: if autoimmune disease is suspected |
| Erythrocyte sedimentation rate |
| Complete metabolic panel, coagulation parameters, uric acid, LDH |
| Patients with anemia: Coombs test, haptoglobin, reticulocyte count and blood smear |
| Targeted-capture, next-generation sequencing of lesional tissue for mutations in RAF-RAS-MEK-ERK pathway (eg, KRAS, MAP2K1): in severe or refractory cases |
| Bone marrow aspirate/biopsy (if cytopenias or abnormal peripheral blood smear are present) |
| Lumbar puncture (for brain lesions inaccessible to biopsy); CSF pleocytosis with emperipolesis visible upon cytologic examination is indicative of RDD |
| Check lesional tissue for PDGFR-α/β and c-kit |
| Germ line mutations in SLC29A3: if familial RDD is suspected |
CSF, cerebrospinal fluid; HEENT, head, eyes, ears, nose, and throat; LDH, lactate dehydrogenase.