A 15-Year-Old Patient With History of Juvenile Idiopathic Arthritis Presenting With a Painful Skin Rash

A 15-year-old girl, a recent immigrant from Colombia, goes to an outpatient pediatric rheumatology clinic to establish care per referral from her primary care physician. The patient is observed to have pain with light touch to her wrist and shoulders unresponsive to her outpatient pain medications as well as poor weight gain and general malaise. She is advised to go to the emergency department for further workup, pain management, and possible initiation of biologic therapies, which would require close monitoring. The patient is admitted to the hospital with a diagnosis of severe autoimmune flare; she is evaluated by the pediatric rheumatologist for a comprehensive autoimmune workup. Physical examination is significant for edema, warmth, and tenderness in more than 5 joints, including the bilateral wrists, knees, ankles, and shoulders. There is no family history of rheumatologic conditions. Magnetic resonance imaging confirms bilateral synovitis and inflammatory arthropathy of the temporomandibular joints.The patient is diagnosed with polyarticular juvenile idiopathic arthritis (JIA) affecting her wrists, knees, ankles, metacarpophalangeal/metatarsophalangeal joints, and lumbar spine. She is started on a 3-day course of steroids (1 g intravenous [IV] methylprednisolone daily), followed by maintenance prednisone (20 mg daily) and methotrexate (25 mg weekly injections). Although the patient does have regular menstrual cycles, initiation of birth control concomitantly with methotrexate is deferred currently because she is not sexually active. She receives an infusion of rituximab (monoclonal antibody targeting the CD20 protein on B lymphocytes) without complications. Symptoms improve after 5 days of hospitalization, and the patient is discharged on naproxen 250 mg twice daily for fever and discomfort with plans for a prednisone taper and follow-up in 6 weeks. Over that time period, she continues to experience periodic flares that occasionally necessitate treatment with a corticosteroid burst.Three months after discharge, the patient presents to the emergency department with excruciating pain and rash. Four days prior, the patient developed a low-grade fever with pruritus and a burning sensation that began on her upper right back and spread to her right chest and axilla. There were no sick contacts or recent travel. On physical examination she is alert and oriented but visibly uncomfortable from a reported “10/10 burning pain.” Vitals reveal a temperature of 37.0 °C, respiratory rate 18 breaths/min, and blood pressure of 137/97. Her body mass index is 18.8 (29th percentile for her age). Skin examination is significant for dense, erythematous bullae and vesicular lesions in the right chest and axillary region, extending to the right upper back (Figure 1). Grayish plaques with scales are visible in some areas of the rash (Figure 2). The rash appears to be limited to the T1 dermatome (Figure 3). Laboratory testing demonstrates a white blood cell of 9100 cells/μL and mild thrombocytosis (platelet count of 435 000/μL). The mother described how the patient had contracted varicella (chickenpox) as a child. Further questioning reveals that the patient received her first varicella vaccine at 12 months of age; however, she did not receive the recommended booster at 4 to 6 years of age. The patient history and physical examination confirm the diagnosis.The differential diagnosis included viral exanthem, JIA exacerbation rash, allergic dermatitis, and hidradenitis suppurativa. Viral exanthem was explored because of the combination of fever with skin rash. Viruses like herpes simplex virus can also cause similar vesicular rashes but typically occur around the mouth or genital regions. Contact dermatitis can also cause similar vesicular rashes; however, the pain and sudden onset of rash without any provoking exposures to known allergens made this diagnosis less likely. Hidradenitis suppurativa can present bullous lesions, especially in the axillary region, which this patient had; however, the patient’s bullous lesions did not appear pus-filled. The dermatomal distribution of the lesions in combination with severe pain led to a clinical diagnosis of herpes zoster (HZ) virus activation, commonly known as shingles.HZ manifests as a reactivation of previously acquired varicella zoster (VZ) virus. Approximately 99% of Americans older than 40 years old have had VZ virus during childhood,1 and approximately 1 million patients experience HZ annually. Of those with past infection with varicella, 1 in 3 will experience HZ.1 The mean age for HZ diagnosis has remained steady at 76.9 years in 1992 and 77.9 years in 2010.2 Since the US Food and Drug Administration’s approval of the varicella vaccine in 1995, the incidence of varicella has decreased dramatically. One study of 4 states from 1990 to 2019 highlighted an average 98.6% decline in incidence.3 Nevertheless, there are still children who remain unvaccinated. Various circumstances can be attributed to their unvaccinated status including socioeconomic barriers to receiving or accessing health care or parental vaccine hesitancy.Although the diagnosis of HZ in the pediatric population is rare, it is not novel. In children, an HZ infection is most associated with an underlying metabolic or neoplastic disorder.4 However, another risk factor for the development of HZ in the pediatric population is an immunocompromised state. In this case report, we focus on highlighting systemic JIA, which is defined with the following criteria: children under the age of 16 years with arthritis in 1 or more joints for at least 6 weeks along with transient rash and fever for 2 weeks duration. Pediatric patients diagnosed with systemic JIA are often managed by a pediatric rheumatologist who may manage longitudinal symptoms through a personalized plan involving corticosteroids, biologic disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs, and physical therapy. Examples of synthetic DMARDs are methotrexate, azathioprine, and cyclophosphamide (drugs that use immunosuppression as the mechanism of action). In a study of rheumatoid arthritis drugs, targeted systemic DMARDs were shown to have a 3.6-fold higher risk of developing HZ compared with control treatment groups5; the exposure-adjusted event rate of HZ for targeted systemic DMARDs was 21.5 vs 7.1 for patients receiving conventional systemic DMARDs. Although this study was done in adults, the same rationale can be applicable to pediatric patients. Additionally, a report on opportunistic infections revealed that children with JIA had an increased risk compared with the control group in rates of acquiring Coccidioides, salmonella, and HZ.6 Almost 20% of all severe or serious infections in patients with JIA receiving immunosuppressive therapies are opportunistic.7 Thus, it is vital to understand the interplay between immunosuppression and opportunistic infections when considering treatment plans for these patients.The novelty in this case report stems from the underlying treatment of a recent JIA exacerbation leading to an overtly immunocompromised state, which presumably is what led to the severity of the patient’s HZ manifestation. A feared complication of HZ infection is progression into disseminated HZ, which is uncommon but more likely in immunocompromised patients.4 The management of a patient who exhibits HZ in addition to severe manifestations of systemic autoimmune-induced symptoms requires a patient-centered, individualized approach.Treatment of HZ involves antiviral medications, analgesia, and rash care. Antivirals such as acyclovir, famciclovir, and valacyclovir are first-line therapies that have been shown to reduce the duration and severity of symptoms, especially when administered within the first 72 hours of the rash onset.3 One question remains: before starting antiviral therapy, what should be done with the patient’s immunosuppressive therapy for underlying autoimmune disease? One study noted that the rates of HZ were similar between patients with JIA who were being treated with methotrexate alone vs with a methotrexate/etanercept combination.8 However, the decision to continue or temporarily halt the JIA medication is one with no clear guideline; the decision is usually guided by rheumatology’s impression of the patient’s full clinical picture. A retrospective multicenter study from the Swiss Pediatric Rheumatology registry reported that half of the participating rheumatologists continued immunosuppressive medications during the HZ manifestation in such cases.9 Others argue that terminating the immunosuppressive medication could prove beneficial, as it allows the immune system to more efficiently clear the HZ outbreak.9Regarding symptomatic management, first-line treatments during a shingles exacerbation include agents like acetaminophen and ibuprofen, which can aid in reducing fever and alleviating pain. However, ibuprofen should be avoided if the pediatric patient is younger than 6 months old. Persistent pain can be treated with opioid medications, particularly when pain is not controlled by more conservative management. Patients who experience postherpetic neuralgia can be managed with a first-line medication such as gabapentin. Rash management involves keeping the skin clean and using topical agents like calamine (which can alleviate itchiness) for symptomatic relief.Lastly, the management of patients with JIA affected by the HZ virus raises the question of what could have been done to prevent the occurrence in the first place. Current guidelines recommend adults receive the VZ vaccine to prevent virus reactivation.10 Current vaccine recommendations are for all adults 50 years of age and older to receive a 2-dose series of the recombinant shingles vaccine. Adults with weakened immune systems are recommended to receive the vaccine series starting at age 18 years.4 There is more ambiguity about the recommendation of the HZ vaccine for pediatric patients, but there is certainly a risk for recurrence. A study following 3042 children with JIA found of the 17 patients who developed HZ, 1 was complicated by a case of recurrent HZ.11 Whether the patient in this case report would benefit from the recombinant zoster vaccination immediately following infection is unclear; however, future administration of the HZ vaccine at age 18 years could reduce the chance of recurrent zoster especially if her immunocompromised state persists.During hospitalization, the patient received 6 days of IV acyclovir; her methotrexate was halted and prednisolone was tapered down from 10 mg to 5 mg twice a day. Pain management included calamine cream, Tylenol, gabapentin, and IV morphine as needed. Her rash worsened during the first 4 days, and she was monitored for signs of disseminated disease, but her rash remained in the T1 dermatome and never crossed midline. By day 7, most of the rash appeared to be crusting over. The patient was transitioned to oral valacyclovir, and she was discharged with a 7-day supply. She had a follow-up appointment with outpatient rheumatology later that same week; we do not have records of exactly when her methotrexate was restarted. Follow-up phone check-in 3 months later showed complete resolution of the rash.SummarySystemic JIA treatment with immunosuppressant agents (such as glucocorticoids and DMARDs) is a risk factor for development of opportunistic infections such as the HZ virus in children with prior varicella infection.Treatment of HZ in pediatric patients with JIA involves antiviral therapy (such as acyclovir) and personalized management of immunosuppressive medications by collaboration between the infectious disease and rheumatology team.Patients with JIA should receive the recombinant HZ vaccine if their immunosuppressive state persists at age 18 years.The recombinant HZ vaccine is safe and efficacious for immunocompromised persons and should be administered as a 2-dose schedule, preferably before administration of immunosuppressive medications to optimize generation of better humoral and cellular immune response.12