Introduction
Methods
Category | Definition |
---|---|
Strength of recommendation (SoR) | |
A | Strongly supports a recommendation for use |
B | Moderately supports a recommendation for use |
C | Marginally supports a recommendation for use |
D | Supports a recommendation against use |
Quality of evidence (QoE)—level | |
I | Evidence from at least one properly designed randomized, controlled trial |
II | Evidence from at least one well-designed clinical trial, without randomization; from cohort- or case-controlled analytic studies (preferably from > 1 center); from multiple time series; or from dramatic results of uncontrolled experiments |
III | Evidence from opinions of respected authorities, based on clinical experience, descriptive case studies, or reports of expert committees |
Quality of evidence (QoE) – index, for level II | |
r | Meta-analysis or systematic review of randomized controlled trials |
t | Transferred evidence, that is, results from different patient cohorts, or similar immune-status situation |
h | Comparator group is a historical control |
u | Uncontrolled trial |
a | Published abstract (presented at an international symposium or meeting) |
Manifestations of HSV-1, HSV-2, and VZV
HSV-1 | HSV-2 | VZV | |
---|---|---|---|
Neurotrophic latency | Ganglion trigeminale, ganglion sacrale | Ganglion sacrale, Ganglion trigeminale | Cranial nerve ganglia, dorsal root ganglia |
Reactivation | Asymptomatic viral shedding Herpes labialis Stomatitisa) Herpes genitalis Oesophagitis a) Hepatitis a) Colitis a) Pneumonitis a) Encephalitis Keratitis | Asymptomatic viral shedding Herpes genitalis Hepatitis a) Meningitis Encephalitis | Herpes zoster b) Disseminated herpes zoster a) Hepatitis a) Pancreatitis a) Pneumonitis a) Meningoencephalitis Cerebral vasculopathy Keratitis, uveitis, retinitis |
Diagnostics
Serology
Clinical situation | Intention | Diagnostic strategy | SoR | QoE | Comments | Reference |
---|---|---|---|---|---|---|
Patients at risk of HSV reactivation (patients with acute leukaemia planned for intensive therapy or other specified patient group) | Diagnosis of prior exposure, to decide about prophylaxis a) | HSV serology (IgG) | B | III | (see text) | |
Patients with suspicion of HSV disease | To diagnose HSV disease | HSV serology (IgM, serial IgG) | D | III | Low sensitivity, time delay | [11] |
To diagnose HSV disease | qPCR for HSV vs. viral culture (mucosal swab, BW, BAL) | A | IItu | qPCR with higher sensitivity, reliability, speed | ||
Patients with stomatitis after (radio-) chemotherapy | To diagnose HSV stomatitis | qPCR for HSV-1 (oral swab) | C | IIu | ||
Patients with clinical diagnosis of herpes genitalis | To diagnose HSV | qPCR for HSV (genital or perianal swab, preferably vesicle content) | A | III | For differential diagnosis | |
Patients suspected for herpes encephalitis | To diagnose HSV encephalitis | qPCR for HSV (CSF) | A | IItu | No exclusion by negative result, particularly if therapy has already started | |
To diagnose HSV encephalitis | HSV IgG (CSF/serum) | C | III | Additionally | ||
Patients suspected for herpes pneumonitis | To diagnose HSV pneumonitis | qPCR (BW, BAL) | A | IIu | HSV DNA may also stem from oropharyngeal sites (see text) | |
Patients suspected for other organ HSV disease | To diagnose HSV visceral disease | qPCR for HSV (organ biopsy) | A | IItu | No exclusion by negative result, particularly if therapy has already started | [48] |
Asymptomatic patients at risk for HSV reactivation | To screen for viral replication | qPCR for HSV-1 (mucosal swab) | D | I | Asymptomatic viral shedding; pre-emptive treatment not recommended |
Clinical situation | Intention | Diagnostic strategy | SoR | QoE | Comments | Reference |
---|---|---|---|---|---|---|
Patients at risk of VZV reactivation (patients with lymphoma or multiple myeloma or other specified patient group) | Diagnosis of prior exposure, to decide about prophylaxisa | VZV serology (IgG) | B | III | ||
Patients with suspicion of VZV disease | To diagnose VZV disease | VZV serology (IgM, serial IgG) | D | III | Low sensitivity, time delay | |
To diagnose VZV disease | qPCR for VZV versus DFA or viral culture (skin swab, vesicle content) | A | IItu | qPCR with higher sensitivity, reliability; qPCR applicable on varying specimen | ||
Patients with typical segmental zoster lesion | To diagnose VZV | qPCR for VZV (skin swab) | C | III | Usually diagnosis on clinical grounds; for differential-diagnosis to HSV | [52] |
Patients with atypical zoster lesion | To diagnose herpes zoster | qPCR for VZV (skin swab) | A | III | [52] | |
To diagnose herpes zoster | qPCR for VZV (saliva) | B | II | Saliva more sensitive than blood | ||
To diagnose herpes zoster | qPCR for VZV (blood) | C | II | |||
Patients with suspected zoster sine herpete | To diagnose VZV disease | qPCR for VZV (blood) | A | II | For rapid diagnosis | |
To diagnose VZV disease | qPCR for VZV (saliva) | B | II | |||
Patients with suspected disseminated zoster | To diagnose VZV disease | qPCR for VZV (blood) | A | III | Not necessary if clinical diagnosis is obvious | [52] |
Patients with zoster ophthalmicus | To diagnose ocular involvement | qPCR for VZV (affected superficial structure of the eye) | A | III | Ophthalmological examination recommended and often sufficient for diagnosis | [52] |
Patients suspected for VZV encephalitis | To diagnose VZV encephalitis | qPCR for VZV (CSF) | A | II | No exclusion by negative result, particularly if therapy has already started | |
To diagnose VZV | VZV IgG (CSF/serum) | C | III | Alternative in cerebral vasculopathy | ||
To diagnose VZV | qPCR for VZV (blood) | C | II | [53] | ||
Patients suspected for VZV pneumonitis | To diagnose VZV pneumonitis | qPCR for VZV (BAL) | A | IIu | No exclusion by negative result, particularly if therapy has already started | [54] |
To diagnose VZV | qPCR for VZV (blood) | B | IIu | [54] | ||
Patients suspected for other organ VZV disease | To diagnose VZV visceral disease | qPCR for VZV (organ biopsy) | A | III | No exclusion by negative result, particularly if therapy has already started | [11] |
To diagnose VZV | qPCR for VZV(blood) | A | III | No exclusion by negative result, particularly if therapy has already started | ||
Asymptomatic patients at risk for VZV reactivation | To screen for viral replication | qPCR for VZV (blood) | D | III | Pre-emptive treatment not recommended | [11] |
Virus detection
Testing of resistance
Contribution of imaging techniques to diagnosis
Pharmacological prophylaxis
Vaccination
Patient groups
Patients with solid tumours
Clinical situation | Intention | Intervention | SoR | QoE | Comments | Reference |
---|---|---|---|---|---|---|
Patients with solid tumours and systemic therapy (in general; for specific risks see below) | To prevent HSV/VZV reactivation | Acyclovir | D | III | Low risk of reactivation | |
Patients with HNSCC, treated with radiochemotherapy | To prevent HSV stomatitis | Acyclovir | C | IIr | [34] | |
Patients with malignancies, taking corticosteroids in high doses long term (> 10 mg PEQ per day for 14 days or longer) | To prevent herpes zoster | Acyclovir | C | IIu | Persisting risk for several months after corticosteroid has been stopped (see text) | [77] |
Patients with acute leukaemia
Clinical situation | Intention | Intervention | SoR | QoE | Comments | Reference |
---|---|---|---|---|---|---|
Patients with AML/high-risk MDS, planned for intensive therapy | To prevent HSV stomatitis and other clinical manifestations of HSV | Acyclovir, valacyclovira | B | IIr | For remission induction chemotherapy (see text) | |
To prevent herpes zoster (and other clinical reactivation of VZV) | Acyclovir, valacyclovira | B | IIr | Particularly in patients with APL treated with arsenic trioxide (see text) | ||
Patients with ALL | To prevent HSV stomatitis and other clinical manifestations of HSV | Acyclovir | B | I | While on treatment | |
To prevent herpes zosterb | Acyclovir | B | III | |||
Patients with MPN, treated with ruxolitinib | To reduce HSV disease | Acyclovir | C | IIu | ||
To prevent herpes zosterb | Acyclovir | B | IIru |
Patients with myeloproliferative neoplasm
Patients with lymphoma
Clinical situation | Intention | Intervention | SoR | QoE | Comments | Reference |
---|---|---|---|---|---|---|
Patients with non-Hodgkin lymphoma, treated with immuno-chemotherapya | To reduce HSV/VZV disease | Acyclovir (valacyclovir)b | B | IIu | Persisting risk for several months after therapy (see text) | |
To reduce mortality | Acyclovir | C | IIah | Together with cotrimoxazol, in patients aged > 60 years | [91] | |
Patients with Hodgkin’s diseasea | To prevent herpes zoster | Acyclovir (valacyclovir) b) | C | III | [89] | |
Patients with CLL receiving immuno-chemotherapya | To reduce HSV/VZV disease | Acyclovir, (valacyclovir) b) | B | IIuh | Persisting risk for several months after therapy (see text) | |
Patients with CLL (and other Non- Hodgkin lymphoma) receiving BTK or BCL2 inhibitorsa | To prevent herpes zoster (to reduce VZV/HSV disease) | Acyclovir, (valacyclovir)b | C | IIu | Of benefit particularly in advanced lines of therapy | |
Patients with CLL (and other Non-Hodgkin lymphoma) receiving idelalisib | to reduce HSV/VZV disease | acyclovir | B | III | High general risk of opportunistic infections, persisting for several months after therapy | |
Patients with MM, receiving bortezomib | To reduce VZV diseasec | Acyclovir, valacyclovir | A B | IIu IIu | d | |
Patient with MM receiving carfilzomib | To reduce VZV diseasec | e.g., acyclovir | A | IIu | d | |
Patients with MM receiving ixazomib | To reduce VZV diseasec | e.g., acyclovir | A | IIh | d | |
Patients with MM receiving lenalidomid | To reduce VZV diseasec | e.g. acyclovir | C | IIh | d | |
Patients with MM receiving daratumumab | To reduce VZV diseasec | e.g. acyclovir | C | IIt | d | |
Patients with MM receiving elotuzumab | To reduce VZV diseasec | e.g. acyclovir | C | IIt | d | |
Patients with MM receiving conventional-dose chemotherapye or other targeted agentsa | To reduce VZV diseasec | e.g. acyclovir | C | IIt | d |