Virus
Medical treatment
HSV
Topical treatment: Aciclovir cream (5 %) five times daily (3–4 hourly intervals) during waking hours for 4 days [7].
Orolabial herpes and genital herpes – primary infection: valacyclovir 1 g orally twice daily during 10 days
Orolabial herpes – recurrence: valacyclovir 2 g orally twice daily only 1 day [7]
Genital herpes – recurrence: valacyclovir 1 g orally daily during 5 days or 500 mg orally twice daily during 3 days
Immunocompromised patient: valacyclovir 1 g orally twice daily until all the lesions have resolved
Eczema herpeticum: valacyclovir 1 g orally twice daily or, in severe cases, acyclovir 5 mg/kg iv, if patient >12 years, or 10 mg/kg, if patient <12 years, every 8 h during at least 10–14 days and until all lesions have resolved
Neonatal: acyclovir 20 mg/kg iv every 8 h during 14–21 days
Resistant HSV and immunocompromised patient: foscarnet 40 mg/kg iv every 8–12 h during 2–3 weeks and all the lesions have resolved
There is no vaccine or drug to prevent or cure [9].
VZV
Gold standards for the treatment of VZV are acyclovir and valacyclovir [38].
Varicella in immunocompetent patient: valacyclovir 20 mg/kg with the maximum of 1 g orally every 8 h during 5 days.
Zoster in immunocompetent patient: valacyclovir 1 g orally every 8 h during 7 days
Immunocompromised (varicella and zoster): acyclovir 10 mg/kg iv every 8 h during 7–10 days and up to the lesions have resolved (in severe cases); valacyclovir 1 g orally every 8 h for 7–10 days (in mild cases); foscarnet 40 mg/kg iv every 8 h until total resolution (in resistant cases)
Varicella-vaccines are efficacious. Different recommendations worldwide [39].
Herpes zoster vaccine is considered safe and effective to reduce the burden and severity of the disease in older adults. It is cost-effective when administered to immunocompetent adults >60 years [10].
For postherpetic neuralgia, a multidisciplinary approach is the best option: prevention strategies including zoster vaccine, antiviral therapy within 72 h of rash onset and pain control. Besides, anticonvulsants, antidepressants, topical lidocaine, capsaicin and opioids can be combined [40].
EBV
Supportive care.
Corticosteroids for complicated cases associated with, for example, severe thrombocytopenia [4].
In patients with lymphoproliferative disease prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ lymphoproliferative disease post-transplant. Cellular therapy targeting EBV on this context is being analysed [11].
CMV
Supportive care of CMV-induced mononucleosis in immunocompetent patients.
CMV-seronegative donors for seronegative recipientes.
For treatment and prophylaxis of CMV infections in immunocompromised patients, the first line options are: ganciclovir iv and valganciclovir oral 14–28 days [41]. Foscarnet, cidofovir and sirolimus are second-line options for resistant cases [42]. Anti-CMV immunoglobulins may be another option for the resistant cases [41–43].
CMV vaccine is not still available [12].
Cellular immunotherapy studies on adaptive immunity, in particular T cells and natural killer (NK), are being conducted [44].
HHV-6
Supportive care.
In the setting of complications in immunocompromised patients, some studies point out foscarnet and ganciclovir but dosages are not consensual [45].
Autologous T cell immunotherapy to prevent post-transplantation viral reactivation is under research [45].
HHV-7
Supportive care.
No consensual treatment strategies.
HHV-8
Several treatment options exist: cryotherapy, radiotherapy, topical alitretinoin, intralesional interferon-α, intralesional and systemic vinblastine, other systemic agents, anti-retroviral therapy for patients with AIDS and even liposomal anthracyclines [46].
Other treatments are still under research.
Psychological Intervention
Some studies have reported that psychological interventions modulate psychological variables connected with skin diseases, including those caused by HHV, with correlated immune changes and therapeutic relevance. Cellular immunity plays a critical role in HHV infection. The assessment of the severity of depressive symptoms and their treatment is correlated with normalization in NK cell activity and lymphocyte proliferation (altered in depressed subjects), improving immune function [23].
Although the studies on psychological interventions for skin diseases due to HHV are still scarce, according to the literature, there has been some evidence for the benefit of cognitive behavior therapy (CBT) and medical hypnosis in patients with skin diseases due to HHV. Both have been suggested as effective for several skin diseases [47].
The core of CBT is a problem-focused psychotherapy about the connection between thoughts, emotions, physical symptoms and behaviors. The disfigurement caused by having a skin disease may lead to stigma and, thereby, to negative thoughts, which are the starting point for depression and anxiety, to unhelpful feelings and behaviors. Additionally, variations of CBT have been successfully used. Therefore, an initial psychological assessment is crucial and even simple CBT can be offered in clinical practice, with proved benefits, for people with low or moderate levels of distress/depression [48]. Thus, with CBT we may stop the vicious cycle commonly seen in patients with psychodermatologic conditions, which is the following: the negative thoughts that people construct about the disease trigger negative feelings, which lead to physical changes (in biological functions, such as altered sleep) and, thereafter, to unhelpful behaviors. Some studies have also found evidence for a biological mechanism behind the clinical benefits. A case-control study performed by Lutgendorf et al. (1997) showed that CBT improved mood disorders and anxiety symptoms in symptomatic HIV-seropositive men and that was correlated with lower herpes simplex virus-type 2 antibody titers [49]. Later, Cruess et al. (2000) showed in a similar case-control study that HSV-2 antibody titers decreased after CBT and this was correlated with a decrease in cortisol/dehydroepiandrosterone sulfate (DHEA-S) ratio levels, reinforcing the knowledge that had been previously suggested by the neuro-immuno-cutaneous-endocrine model by O’Sullivan et al. (1998) [2, 50].
On the other hand, hypnosis is a psychological intervention that explores inner concentration and focused attention. Neurophysiological studies have shown that hypnosis modifies self-awareness as well as environmental consciousness, involving therefore internal and external brain networks [51]. In a study performed by Fox et al. (1999) psychological and immunological parameters were measured prior and after hypnotherapy in a group of patients with recurrent genital herpes simplex virus. They saw a significant reduction in the number of reported episodes of recurrent genital herpes simplex virus as well as an increase in the numbers of CD3 and CD8 lymphocytes after hypnosis. Moreover, the patients showed significant rises in natural killer (NK) cell counts and HSV specific lymphokine activated killer (LAK) cells activity. Furthermore, there was a correlation between those findings and lower anxiety scores [52]. More recently, through a case-control study with patients suffering from recurrent orofacial herpes infections, Pfitzer et al. (2005) concluded that with a hypnosis program, disease severity could be significantly reduced. They could also conclude that, in patients with recurrent orofacial herpes infections, a treatment only targeted to the physical changes was not enough. There was an important correlation between a deep analysis of psychological factors, such as person’s sensuality, and treatment success [53]. This last point highlights the relevance of a deep analysis of the patient’s life history in psychodermatologic diseases. This had been already suggested by Herman Musaph [54], one of the fathers of psychodermatology, and it is an important issue crossing all psychological interventions.
All in all, a truly biopsychosocial approach for patients suffering from skin manifestations of HHV should explore psychosocial factors and psychopathology. For example, as it was mentioned, postherpetic neuralgia has a multidimensional mechanism, having sensory and affective elements. Because psychological interventions can affect cortisol release, they also influence the course of chronic pain. CBT has evidence to support its use in the treatment of chronic pain conditions, including postherpetic neuralgia. It helps to manage anxiety, depression, feelings of hopelessness and it also provides pain management strategies. The patient learns how to cope with stress, helping to relax and control the pain. Through CBT the pain-tension-anxiety cycle is then stopped, with correlated biochemical beneficial changes [18].
Thereby, as for other skin diseases, a psychological examination should be included in clinical practice. This would help to select the best psychological intervention (evidence-based) to treat mental health problems related to the skin disease. Dermatologists can take psychosocial history, determine the scores of anxiety or depression, the impact of the skin diseases on quality of life and start the process of engagement with psychological treatment. Table 20.2 suggests an algorithm outlining psychodermatologic approach to the patient with skin disease and cutaneous symptoms due to HHV. Some psychological interventions can be conducted in dermatologic practice (such as simple CBT) while others may need a referral to a psychiatrist or a psychologist [48].
Table 20.2
Psychodermatologic approach of the patient with skin conditions due to HHV
Initial assessment by a dermatologist |
---|
The scores of anxiety and depression should be determined. Several scales are available. For example: “The Hospital Anxiety and Depression Scale” [55]; |
If normal, no psychological intervention is required (only medical treatment); |
If low, moderate or severe, a psychological intervention should be considered. |
For patients with low levels of anxiety and depression, the psychodematologic approach can be conducted by the dermatologist. |
Patients with moderate and severe levels of anxiety and depression would ideally require a psychodermatology team (dermatologist, psychiatrist, psychologist and nurse). |
References
1.
2.
O’Sullivan R, Lipper G, Lerner E. The neuro-immuno-cutaneous-endocrine network: relationship of mind and skin. Arch Dermatol. 1998;134(11):1431–5.PubMed