230 Oral Mucositis Related Topic Nausea and Vomiting (p 111) EMETOGENIC LEVELS OF INTRAVENOUSLY ADMINISTERED ANTINEOPLASTIC AGENTS HIGH RISK (>90%) carmustine, cisplatin, cyclopho sphamide (>1.5 g/m2), dacarbazine, mechloretha mine, streptozocin MODERATE RISK (31 90%) carboplatin, cyclopho sphamide (!1.5 g/m2), cytarabine (>1 g/m2), daunorubicin, doxorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, oxaliplatin LOW RISK (10 30%) bortezomib, cetuximab, cytar abine (!1 g/m2), docetaxel, etoposide, fluorouracil, gemcitabine, ixabepilone, lapatinib, methotrexate, mitomycin, mitoxantrone, paclitaxel, pemetrexed, topotecan, temsirolimus, trastuzumab MINIMAL RISK (24 h) asso ciated with cisplatin, cyclophosphamide, ifosfamide at higher doses and doxorubicin NK1 antagonists, 5HT3 antagonists, and steroids are all effective CHRONIC NAUSEA AND VOMITING unlikely to be due to chemotherapy alone Multi factorial interven tions required Avoid long term use of 5HT3/NK1 antagonists MANAGEMENT (CONT’D) TREATMENT OVERVIEW FOR PREVENTING ACUTE AND DELAYED CINV Risk NK1 5HT3 Steroid Etca antagonist antagonist Highb X X X X Moderate X X X Low X X Minimal X a choices include metoclopramide 10 mg PO q4h PRN and prochlorperazine 10 mg PO q4h PRN b highly emetogenic chemotherapy or doxorubicin/ cyclophosphamide (AC) combination chemotherapy TREATMENT ISSUES HIGH RISK CHEMOTHERAPY OR AC COMBINATION CHEMOTHERAPY aprepitant 125 mg PO on day 1, then 80 mg PO days 3, PLUS ondansetron 12 mg IV or 16 24 mg PO on day 1, PLUS dexamethasone 12 mg PO/IV on day 1, then mg PO days PLUS metoclo pramide 10 mg PO q4h PRN or prochlorperazine 10 mg PO q4h PRN MODERATE RISK CHEMOTHERAPY ondansetron mg IV or mg PO BID on day 1, then mg PO BID on days 3, PLUS dexamethasone 12 mg PO/IV on day 1, then mg PO or mg PO BID days PLUS metoclopramide 10 mg PO q4h PRN or prochlorpera zine 10 mg PO q4h PRN LOW RISK CHEMOTHERAPY dexamethasone mg PO/IV day PLUS metoclopramide 10 mg PO q4h PRN or prochlorperazine 10 mg PO q4h PRN LOW, RISK CHEMOTHERAPY metoclopramide 10 mg PO q4h PRN or prochlorperazine 10 mg PO q4h PRN NOTE for patients with significant nausea and vomiting despite proper oral antiemetic use, consider admission for intravenous hydration and medication administration Oral Mucositis PATHOPHYSIOLOGY RISK FACTORS FOR ORAL MUCOSITIS PERSONAL younger age, poor oral hygiene, smok ing, alcohol use CHEMOTHERAPY bleomycin, capecitabine, chlor ambucil, cytarabine, doxorubicin, etoposide, meth otrexate, vinblastine, fluorouracil TARGETED AGENTS RAD001 RADIATION head and neck region COMPLICATIONS OF ORAL MUCOSITIS severe pain, bleeding, superinfections (bacteremia, febrile neutropenia) NCI CTC GRADING V4.0 Grade Oral mucositis Asymptomatic or mild symptoms; intervention not indicated Moderate pain; not interfering with oral intake; modified diet indicated Severe pain; interfering with oral intake Life threatening consequences; urgent intervention indicated 231 Chemotherapy-Induced Diarrhea MANAGEMENT (CONT’D) MANAGEMENT CRYOTHERAPY sucking on ice chips during che motherapy is a reasonable preventative strategy for patients on fluorouracil, edatrexate, or high dose melphalan ORAL HYGIENE soft tooth brush, flossing, mouth rinses q4h (0.9% saline, baking soda, or salt and baking soda solution by mixing one teaspoon of baking soda and half teaspoon of salt in 1/L of water), denture care (if applicable) DOSE ADJUSTMENTS dose reduction or treatment termination may be considered in severe cases SUPPORTIVE MEASURES ensure adequate hydra tion and monitor nutritional intake Assess patients for diarrhea as well Providing optimal pain control is key TOPICAL ANALGESIA / generally includes lidocaine for pain control For a 100 mL solution, mix hydrocortisone 25 mg, glycerin 95% mL, normal saline 52 mL, lidocaine 2% 25 mL, and nystatin 2083,300 IU or 20.833 mL Use 10 mL squish and spit q4h q6h MORPHINE SULFATE MOUTHWASH mg/mL in 15 mL of water, swish and spit, q4h to q6h LIDOCAINE VISCOUS 2% 10 mL, swish and spit, q4h PRN SYSTEMIC OPIOIDS morphine mg IV q4h PRN or 10 mg PO q4h PRN, titrating up as needed INFECTIONS oral candidiasis (nystatin 500,000 IU swish and swallow QID, clotrimazole troches, or fluconazole), HSV infections (acyclovir or valacy clovir after cultures taken) MAGIC MIRACLE MOUTHWASH Chemotherapy-Induced Diarrhea PATHOPHYSIOLOGY RISK FACTORS FOR CHEMOTHERAPY INDUCED DIARRHEA CHEMOTHERAPY fluorouracil, capecitabine, irino tecan (active metabolite SN 30), cisplatin, docetaxel, paclitaxel, doxorubicin, cyclophosphamide, metho trexate, cytosine arabinoside, and topotecan TARGETED AGENTS imatinib, erlotinib, sunitinib, sorafenib NCI CTC GRADING V4.0 Grade Chemotherapy Induced Diarrhea Increase of 38.38C [!1018F], >3 days, neutrophil count 500/mm3 See p 234 for details HIV-RELATED FUO HIV patients, !38.38C [!1018F], duration !3 weeks for outpatients or !3 days for inpatients FEVER, NYD persistent fever that has not yet met the definition for FUO CLINICAL FEATURES HISTORY pattern and duration of fever, associated symptoms (cough, dyspnea, hemoptysis, chest pain, diarrhea, abdominal pain, dysuria, urethral discharge, hematuria, neck stiffness, headache), rash (palpable purpura, exanthem), exposure (food, water, plants, animals, insects, infected human secretions), weight loss, night sweats, travel history, sexual history, HIV risk factors, immunizations, past medical history (rheumatologic disorders, malignancy, alcohol), medications PHYSICAL vitals (tachycardia, tachypnea, hypoten sion, fever, hypoxemia), oral ulcers, lymphadenopa thy, nuchal rigidity, respiratory and cardiac examina tion (murmurs), temporal artery, abdominal examination (hepatosplenomegaly), prostate exami nation, skin lesions (morphology, distribution), tick bite marks, joint examination PATHOPHYSIOLOGY INVESTIGATIONS DEFINITIONS FEVER OF UNKNOWN ORIGIN CLASSIC DEFINITION (FUO) (1961) !38.38C [!1018F], duration !3 weeks, diagnosis uncertain after days of investigation in hospital BASIC CBCD, lytes, urea, Cr, AST, ALT, ALP, bilir ubin, LDH, CK, serum protein electrophoresis, urinalysis, ESR, CRP, ANA, ENA, RF, C3, C4, ANCA, cryoglobulin LABS D Hui, Approach to Internal Medicine, DOI 10.1007/978 4419 6505 8, ể Springer ScienceỵBusiness Media, LLC 2006, 2007, 2011 233 234 INVESTIGATIONS (CONT’D) blood C&S (including Mycobac teria), sputum Gram stain/AFB/C&S, urine C&S, stool C&S, O&P, serology (HBV, HCV, HIV, mono spot, CMV IgM, endemic fungi) IMAGING CXR, echocardiogram (if suspect endocarditis), CT chest/abd/pelvis as guided by symptoms SPECIAL ECG TUBERCULIN SKIN TEST BIOPSY affected tissue MICROBIOLOGY Fever and Rash DIAGNOSIS AND PROGNOSTIC ISSUES DIAGNOSIS the most important diagnostic strat egy is a careful history and physical examination with frequent reassessment PROGNOSIS up to 30 50% will not have a diag nosis despite detail workup; adults who remain undiagnosed have good prognosis MANAGEMENT EMPIRIC ANTIBIOTICS ONLY if suspect infectious etiology and therapy cannot be delayed due to sever ity of patient’s disease (see EMPIRIC ANTIBIOTICS p 257) In general, therapeutic trials of antimicrobials or steroids are discouraged TREAT UNDERLYING CAUSE Fever and Rash DIFFERENTIAL DIAGNOSIS INFECTIONS scarlet fever, toxic shock syndrome, staphylococcal scalded skin syn drome, acute rheumatic fever (erythema mar ginatum, subcutaneous nodules) GRAM-NEGATIVE COCCI meningococcemia (pur pura), disseminated gonococcal infection GRAM-NEGATIVE BACILLI Salmonella typhi, Pseudo monas (ecythema gangrenosum), Vibrio vulnificus GRAM POSITIVE COCCI ENDOCARDITIS Borrelia burgdorferi (Lyme erythema migrans), Treponema pallidum (chancre, second ary syphilis) RICKETTSIAL Rocky Mountain spotted fever, ehr lichiosis, typhus VIRAL EXANTHEM acute HIV, mononucleosis, rubella, measles, roseola, erythema infectiosum, chickenpox, shingles, coxsackie virus, echovirus FUNGAL Blastomyces, Coccidioides, Histoplasma RHEUMATOLOGIC SEROPOSITIVE lupus, dermatomyositis SERONEGATIVE inflammatory bowel disease, reactive arthritis VASCULITIS Wegener’s, polyarteritis nodosa BEHCET’S DISEASE MALIGNANCY lymphoma, leukemia, metastatic, paraneoplastic MEDICATIONS penicillins, cephalosporins, sulfas, barbiturates, phenytoin, procainamide, quinidine OTHERS sarcoidosis, erythema nodosum; Sweet’s syndrome (acute febrile neutrophilic dermatosis) SPIROCHETES CLINICAL FEATURES SETTINGS AGE viral exanthems, scarlet fever, and acute rheumatic fever are more likely in children Mono nucleosis is more common in young adults SEASON tick borne diseases are more common in spring and summer Coxsackie virus and echovirus are more common in summer and fall Meningo coccus and parvovirus are more common in winter and spring GEOGRAPHIC LOCATION Lyme disease in Pacific northwest, the Midwest, and the northeast USA and some southern Canadian locations RMSF in south central and Atlantic states Ehrlichiosis in midwestern, south central, and southeastern states Tularemia in western, southeastern, and south central states and Canada Relapsing fever (Borrelia hermsii) in mountainous areas of the western USA Endemic fungal infections include Blastomyces dermatitidis (southeastern states, Manitoba, and Ontario), Coccidioides immitis (southwestern states), and Histoplasma capsula tum (Mississippi, Ohio River valleys, and Quebec) HISTORY pattern and duration of fever, associated symptoms (cough, dyspnea, chest pain, diarrhea, abdominal pain, dysuria, urethral discharge, neck stiffness, headache), rash (prodrome, location, pro gression, treatment), exposure (food, water, plants, animals, infected human secretions), weight loss, night sweats, travel history, sexual history, immuniza tions, past medical history (rheumatologic disorders, malignancy), medications ... baseline; mild increase in ostomy output compared to baseline Increase of stools per day over baseline; moderate increase in ostomy output compared to baseline Increase of !7 stools per day over baseline;... human secretions), weight loss, night sweats, travel history, sexual history, HIV risk factors, immunizations, past medical history (rheumatologic disorders, malignancy, alcohol), medications PHYSICAL... coxsackie virus, echovirus FUNGAL Blastomyces, Coccidioides, Histoplasma RHEUMATOLOGIC SEROPOSITIVE lupus, dermatomyositis SERONEGATIVE inflammatory bowel disease, reactive arthritis