Patterns and Treatment of Post-Herpetic : A Case Study Kaylie Pierce,* Kathryn Wanat,* Stephanie Egwuatu,* Carolyn Withee,* Nathaniel Allen-Slaba,* Manon Begert,* Megumi Sugita,* James Keene, DO,** Michael Scott, DO,*** Holly Novion,**** Dan Selski, DO,***** Michele McCarroll, DO***

*Osteopathic Medical Student III, College of Osteopathic Medicine, Pacific Northwest University of Health Sciences, Yakima, WA **Interim Chair, Department of Osteopathic Principles and Practice, College of Osteopathic Medicine, Pacific Northwest University of Health Sciences, Yakima, WA **Assistant Professor, Department of Clinical Medicine, College of Osteopathic Medicine, Pacific Northwest University of Health Sciences, Yakima, WA ****Medical Assistant, Seattle Dermatology Center, Seattle, WA *****Assistant Professor, Department of Anatomy, College of Osteopathic Medicine, Pacific Northwest University of Health Sciences, Yakima, WA

Disclosures: None Correspondence: Kaylie Pierce, College of Osteopathic Medicine, Pacific Northwest University of Health Sciences; Butler-Haney Hall; 200 University Parkway, Yakima, WA 98901; Ph: 509-499-1142; [email protected]

Abstract Post-herpetic neuralgia (PHN) results from a herpes zoster complication in the elderly, with variable onset and presentation of nerve . Diagnostic criteria of post- herpetic neuralgia include onset of pain persisting for greater than three months with or without the persistence of a maculopapular rash and vesicular eruptions along dermatomes. Understanding PHN is useful for early diagnosis and treatment to minimize the severity of pain. To properly diagnose PHN, clinical symptoms, risk factors, and for varicella zoster are analyzed. Studies demonstrate that preventative measures, including early varicella-zoster in children and vaccination in adults over 60 years with live and attenuated , were likely to reduce post-herpetic neuralgia by 66.5%. Osteopathic treatment options, including indirect manipulative techniques, can help alleviate the pain caused by PHN. Thus, by creating an understanding of prompt treatment and prevention, we may reduce the overall risk and severity of PHN.

About 20% of patients infected with herpes zoster affected with PHN and the health care system Introduction 1 Postherpetic neuralgia (PHN) is a common will experience PHN with significant morbidity, as a whole. complication following reactivation with with elderly patients (those over 60 years) most 5 Postherpetic neuralgia (PHN) is a painful human herpesvirus 3 (HHV-3) or varicella zoster often affected. Risk factors for developing PHN neuropathic syndrome lasting more than three virus (VZV). This reactivation is referred to as include worsening, acute zoster pain, increased 1,2 age, a more severe eruption at presentation, months caused by reactivation of dormant herpes zoster and presents as a blistering, painful 6 3 (VZV) in sensory ganglia of rash in the affected dermatomes Figure( 1). Risk and the presence of a painful prodrome. The cranial or spinal nerves. Those affected by PHN factors for reactivation of the virus, commonly annual incidence of herpes zoster is about 3.4 cases per 1,000 persons; in those over 90 years report severe interference in their daily lives known as shingles, include autoimmune disease, 1,4 2 physically and subsequently psychologically. immunomodulation, and advanced age. In most of age, the incidence rate increases to 11 cases 6 Recognizing the implications of PHN may patients, the painful vesicular rash resolves within per every 1,000 persons. Of note, the rate of benefit early recognition, diagnosis, and a few weeks; however, in some patients the pain reinfection in immunocompetent patients is therapeutic treatment. associated with the rash persists long after the less than 6%. PHN can present as persistent rash has dissipated. If pain continues for greater “burning,” “stabbing,” “electric,” or “shooting” than three months after the rash has resolved, pain along a single affected . Physical Case Report 4 exam findings include increased or decreased A 95-year-old male was examined seven days after it is termed PHN. The pain is believed to be a vesicular-bullous rash occurred on the right side generated by nerve damage, specifically to the sensation, scarring, (pain from stimuli that don’t usually cause pain, such as a light of his chest and back (Figures 2, 3). He complained trigeminal nerve and geniculate or dorsal root of severe pain in the involved areas as well as the ganglion, where the virus remains dormant after touch with a cotton swab or clothing touching 2 right aspect of his head. Interestingly, he stated he the initial infection. the affected area), mechanical (heightened sensitivity to mechanical stimulus had been vaccinated for herpes zoster. or pain) and/or altered autonomic function.7 Diagnosis: Multiple dermatomal herpes zoster PHN treatment options are limited, and many (T₃-T₆) with associated neuralgia. patients express dissatisfaction with treatment outcomes. This presents an issue for the Treatment: Due to extensive involvement and population of patients experiencing decreased severe discomfort, the patient was prescribed oral quality of life, psychological wellbeing, and antiviral 500 mg TID and prednisone 5 physical functioning1 due to long-standing pain.8 mg TID for 10 days. PHN may play a role in the loss of independent functioning and lead to an increased need for a Results: Ten days later, follow-up exam showed higher level of care, which results in suffering considerable improvement of the vesicular-bullous and a disproportionate burden on both those

Figure 1. Progression of shingles: A cluster of small bumps (1) turns into blisters (2) that resemble lesions, fill with pus, break open (3), crust over (4), and finally disappear. The process takes four to five weeks, after which postherpetic neuralgia may occur, thought to be Figure 2. Herpes zoster of the right aspect of Figure 3. Herpes zoster of the right aspect of caused by nerve damage (5). the chest before treatment. the back before treatment.

PIERCE, WANAT, EGWUATU, WITHEE, ALLEN-SLABA, BEGERT, SUGITA, KEENE, SCOTT, NOVION, SELSKI, MCCARROLL 7,8 lesions (Figures 4, 5) but marked post-herpetic shingles once they are 50 years or older. This References neuralgia over the affected dermatomes as well as vaccine has demonstrated the ability to reduce the 1. Drolet M, Brisson M, Schmader KE, et al. The dermatomes of the right trigeminal nerve and T₂ zoster-related burden of illness and the incidence of impact of herpes zoster and postherpetic neuralgia of the right arm. both zoster and PHN. Widespread vaccination could on health-related quality of life: a prospective study. significantly reduce infection, by a quarter of a million CMAJ. 2010 Nov;182(16):1731-6. cases annually, lowering both consequential costs and Discussion 8 The classic clinical presentation of a herpes zoster morbidity associated with VZV. 2. Gilden D, Nagel MA, Mahalingam R, et outbreak is a maculopapular rash followed by a painful 4 al. Clinical and molecular aspects of varicella vesicular eruption in the affected dermatomes. This PHN is challenging to treat. Choice of medication(s) is zoster virus infection. Future Neurol. 2009 may be accompanied by pain, itching, , guided by a patient’s response to medication, preference, Jan;4(1):103-17. and/or allodynia.5 Usually the rash and associated comorbidities, and drug adverse effects.11 Treatment symptoms resolve within a few weeks, but a small options are aimed to attack the multiple mechanisms of 3. Wei JJ, Chotai S, Sivaganesan A, Archer KR, subset of patients may present with pain that disease. Combination therapy has been the standard in Schneider BJ, Yang AJ, Devin CJ. Effect of pre- continues for three months or more following the clinical practice, although there is no data that evaluates 2 injection use on post-injection patient- resolution of the vesicular eruption. This condition a synergistic or additive benefit. Currently, the first line reported outcomes following epidural steroid is defined as postherpetic neuralgia (PHN). of treatment includes and patch injections for radicular pain. Spine J. 2018 5%, as they demonstrate tolerability profiles. In the past, May;18(5):788-96. Clinically, the presentation of PHN is similar to that tricyclic antidepressants were considered the first-line 11 of a herpes zoster outbreak, but the painful symptoms treatment for PHN. In addition to and 4. Campbell SM, Winkelmann RR, Walkowski typically persist for months to years. The quality of tricyclic antidepressants, oral regimens have included S. Osteopathic Manipulative Treatment: Novel the pain in the affected areas is often described as , , steroids, and NSAIDS. Pregabalin 9 Application to Dermatological Disease. JCAD. burning, stabbing, or electric. Because many of the and opioids have been used for treatment of resistant 2012 Oct;5(10):24-32. symptoms of PHN are sensory, a neurologic exam PHN. Topical treatments have been used, often in testing dermatomal sensation bilaterally may be combination with oral medications like clonidine, 5. Lapolla W, DiGiorgio C, Haitz K, Magel G, useful in assessing patients with suspected PHN. gabapentin, , diclofenac, amitriptyline, opioids, Mendoza N, Grady J, Lu W, Tyring S. Incidence of Age and past medical history may also provide useful ketamine, and botulinum toxin type A. Both topical and postherpetic neuralgia after combination treatment clues in the diagnosis of PHN. Incidence of PHN oral treatments have had varying and limited degrees of with gabapentin and valacyclovir in patients increases with age, affecting just 8% of patients aged success in pain management. with acute herpes zoster open-label study. Arch 50 to 54 years compared with 21% of patients aged 80 Dermatol. 2011 Apr;147(8):901-7. to 84 years.3 PHN may also occur more frequently in New and alternative therapies show promising results patients who suffered more severe symptoms in the in pain management and control of PHN. Physical 6. Yawn BP, Saddier P, Wollan PC, St Sauver JL, acute phase of infection, and some evidence suggests therapy, dry needling, trigger-point injections, and Kurland MJ, Sy LS. A population-based study of the incidence of PHN increases among patients with percutaneous nerve stimulation have been used as the incidence and complication rates of herpes 10 10 other chronic diseases, such as . alternative therapies for some patients. A newer zoster before introduction. Mayo treatment option is narrowband ultraviolet B Clin Proc. 2007 Nov;82(11):1341-9. The optimal treatment of PHN is prevention. The (nbUVB) phototherapy.1 It may prevent or decrease herpes zoster vaccine (HZV) boosts cell-mediated the pain of PHN by suppressing inflammatory 7. Fazio S. Postherpetic Neuralgia. New Eng. J. immunity to both VZV and HZ. Children born after response surrounding sensory due to HZ. Med NOW [blog]. 2014 Oct 17. [cited 2017 Sept 1995 should receive the VZV vaccine and avoid those Low-level laser therapy (LLLT) is another approach 14]. Available from: https://blogs.nejm.org/now/ affected with chicken pox. For those infected with VZV currently under review. Use of low-level laser therapy index.php/postherpetic-neuralgia/2014/10/17/. as a child, the latent VZV can cause HZ and PHN. within the first five days of HZ eruption significantly The best prevention for these patients, as long as they reduces the incidence of postherpetic neuralgia. LLLT 8. Betts RF, Vaccination strategies for the prevention are immunocompetent, is to receive the live attenuated may have the ability to prevent PHN, but further well- of herpes zoster and postherpetic neuralgia. J Am designed, randomized controlled trials are required.12 Acad Dermatol. 2007 Dec;(6 Suppl):S143-7.

It has been shown that patients with PHN exhibit 9. Kost RG and Straus SE. Postherpetic Neuralgia- myofascial pain, so osteopathic manipulative therapies Pathogenesis, Treatment, and Prevention. N Engl J may provide relief. Indirect techniques such as Med. 1996 July;335:32-42. counterstain, which positions stressed tissues at a point of balance and allows myofascial tissues to relax, 10. Johnson RW and Rice ASC. Postherpetic may facilitate relief of tender points and alleviate pain.4 Neuralgia. N Engl J Med. 2014 Oct; 371:1526-33. Indirect treatments may offer significant benefits to some patients when compared to the effectiveness and 11. Tyring S. Management of herpes zoster and risks associated with pain medications. postherpetic neuralgia. J Am Acad Dermatol. 2007 Jul;57:S136-42. PHN is the most common complication of herpes Figure 4. Herpes zoster of the right aspect of zoster disease, affecting up to one third of the 12. Chan YT, et al. Early application of low-level the chest after 10 days of treatment. approximately 1 million VZV patients in the United laser may reduce the incidence of postherpetic States. While not fatal, patients experiencing PHN neuralgia (PHN). J Am Acad Dermatol. 2016 have been shown to experience poor quality of life Sep;75(3):572-7. and dissatisfaction with treatment. 13. Brzezinski P, Cywinska E, Chiriac A. Treatment Research has shown that the best way to prevent of Postherpetic Neuralgia Using Narrow Band PHN is to avoid VZV infection in the first place. Ultraviolet B Radiation (UVB). Mædica. 2015 For children, this is accomplished via the chickenpox Sep;10(3):276-9. vaccination; for adults over age 50 who had chickenpox as children and now have latent VZV, vaccination 14. Progression of shingles. United States [cited: with the live attenuated shingles vaccine has resulted 2017 Sept 14]. Available from https://web.archive. in a 61.1% reduction in VZV disease reactivation.2 org/web/20010611001546/http:/www.fda.gov/ fdac/features/2001/301_pox.html. Emerging studies show evidence of relief through the use of phototherapy, physical therapy, dry needling, trigger-point injections and percutaneous Figure 5. Herpes zoster of the right thoracic nerve stimulation, and indirect osteopathic region of the back after 10 days of treatment. techniques may help alleviate pain.1,4,13

PATTERNS AND TREATMENT OF POST-HERPETIC NEURALGIA: A CASE STUDY