Complex regional pain syndrome-like symptoms during herpes zoster

Complex Regional Pain Syndrome (CRPS) associated with herpes zoster (HZ) was first reported by Sudeck in 1901 (Sudeck, 1901) and is recognized clinically. However, only 13 cases have been published in the literature, and nothing is known about the incidence, prevalence, or natural history (Chester, 1992; Foster et al., 1989; Grosslight et al., 1986; Ketz and Schliack,1968; Kishimoto et al., 1995; Querol and Cisneros, 2001; Sudeck, 1901; Visitsunthorn and Prete, 1981). The aim of the present study was to determine the prevalence of CRPS-like symptoms in a prospectively gathered cohort of subjects with HZ and to follow the natural history of their pain and sensory disturbance during the first 6 months after onset of HZ. Subjects were evaluated at four time points after HZ: 2-6 weeks, 6-8 weeks, 3 months, and 6 months. Only subjects aged 50 or older with pain VAS ratings of >/=20/100 at 2-6 weeks were eligible. The first (screening) visit included a neurological and physical examination that was updated at each subsequent visit. Assessments included ratings of pain intensity, allodynia severity, and rash severity. The neurological exam included determination of presence or absence of the following CRPS-like symptoms: (1) increased sweating, (2) color changes, (3) skin temperature changes, (4) weakness of the affected area based on physical exam, (5) edema, and (6) extension of CRPS-like symptoms outside the affected dermatome. For subjects with HZ in dermatomes that can include the limbs (C4-T2 and L1-S2), extremity involvement was considered present if allodynia or rash extended beyond the neck of the humerus (upper extremity), the inguinal ligament (anterior lower extremity), or gluteal sulcus (posterior lower extremity). Involvement of the extremity was considered proximal if neither HZ rash nor allodynia extended past the elbow (upper extremity) or knee (lower extremity). Of the first 75 subjects recruited, 25 had HZ outbreaks in dermatomes that extended into the extremities (C4-T2 and L1-S2). In this group, 8 subjects had no extremity involvement, 8 had proximal extremity involvement, and 9 had distal extremity involvement. Subjects with distal extremity HZ reported more pain across the four visits (p < 0.05). At 3 months, more subjects with distal extremity involvement met criteria for PHN (8 out of 9, 89%), while only 4 out of 8 (50%) with proximal involvement and 2 out of 8 (25%) of subjects without extremity involvement met criteria for PHN (Chi-square test: p < 0.05). Only 25 out of the remaining 50 (50%) subjects with outbreaks in dermatomes that do not include the extremities met criteria for PHN at 3 months (Chi-square test: p < 0.05). Six months after onset of HZ, 6 out of 9 subjects with distal extremity involvement met PHN criteria compared with 2 out of 8 (25%) with proximal involvement and 2 out of 8 (25%) without extremity involvement (Chi-square test: p = 0.12). Fifteen out of 50 (30%) subjects with outbreaks in dermatomes that do not include the extremities met criteria for PHN (Chi-square test: p < 0.05). No subject had all six CRPS-like symptoms. Of the 17 subjects with extremity involvement, 9 subjects had '0-2 CRPS-like symptoms' and 8 had '3-5 CRPS-like symptoms'. None of the eight subjects without extremity involvement had any CRPS-like symptoms. Of the 50 subjects with HZ outside the extremity, only one had abdominal weakness. Pain ratings were higher in subjects with '3-5 CRPS-like symptoms'. More subjects with '3-5 CRPS-like symptoms' met criteria for PHN at 3 months (7 out of 8, 88%), compared to 5 out of 9 (55%) of subjects with '0-2 CRPS-like symptoms' (p = 0.07). At 6 months, 2 out of 9 (22%) of subjects with '0-2 CRPS-like symptoms' met criteria for PHN, compared with 6 out of 8 (75%) of subjects with '3-5 CRPS-like symptoms' (Chi-square test: p < 0.03). Two case-reports are presented. In summary, the occurrence of CRPS-like symptoms is common in subjects with HZ outbreaks affecting the extremity, particularly if the distal extremity is involved. It is uncertain if the pathophysiology underlying the CRPS-like symptoms observed in this study is similar to that of CRPS from other causes, or if it is relatively specific to HZ. Development of PHN is common in subjects who have experienced CRPS-like symptoms. More aggressive preventive treatments may be justified in this high-risk subset of HZ subjects to prevent development of PHN. Prospective randomized controlled studies are needed to determine which subjects are most likely to benefit and when treatment should begin.