Release of Cervical Muscle Tension Improves Psychological Stress and Symptoms of Moderate-to-Severe Atopic Dermatitis: a Case Series with 20 Patients

This study included 21 consecutive patients with moderate-to-severe AD examined at the Hosono Clinic, Tokyo, Japan, from July 2019 to December 2020. Patients were eligible to enroll in this study according to the following inclusion criteria: age ≥ 18 years; visual analog scale (VAS) score for pruritis of 50 mm, which has a range of 0–100 mm, with higher scores indicating worse itching [10]; a score of 3 (moderate) or 4 (severe) on the Investigator’s Global Assessment (IGA), which ranges from 0 to 4, with higher scores indicating worse disease severity [11]; and a score of more than 10 on the Eczema Area and Severity Index (EASI; scores range from 0 to 72, with higher scores indicating more severe disease) [12]. Patients were excluded if they had received any of the following: systemic treatment for AD within 4 weeks before participating in this study; topical calcineurin inhibitors or very potent or potent topical glucocorticoids within 2 weeks prior to the study; or moderately potent or mild topical glucocorticoids or antihistamines (systemic or topical) within 1 week before the study. None of the patients received ultraviolet radiation therapy during this period.

The patients were treated to release cervical muscular tension using Spineliner SA201 (Sigma Inc., Cranberry Township, PA, USA) [13], which can be used as an adjunct to osteopathic manipulative treatment [14]. The treatment was executed by the stimulation of resonance oscillation of the muscles at all contact points, which could be practiced in a single visit to the clinic. Each treatment session took approximately 10–15 min and was practiced once to twice a week for 3 months. Each patient received a total of 15 treatments. All patients discontinued topical corticosteroid treatments before this study. When rescue therapy was needed, we were prepared to use topical corticosteroids, but it was not required.

The outcome measures and time schedules of this study are presented in Table 1. All the outcome measurements were evaluated before initiating the treatment. Patient-reported outcomes in this study included the VAS for pruritis, and the Patient-Oriented Eczema Measure (POEM), ranging from 0 to 28, with higher scores indicating worse severity [15]. Additionally, the minimal clinically important difference (MCID) in the POEM score has been estimated as a change of 3.4 points [15]. The 5-D itch scale ranges from 5 to 25, with higher scores indicating a greater itching effect [16]. AD severity was assessed using EASI; a change of 6.6 points in the EASI score is the estimated MCID [15]. Additionally, IGA, which is scored from 0 (clear) to 4 (severe), and body surface area (BSA) affected by AD were also used. Hematological parameters were assessed, which included serum levels of thymus and activation-regulated chemokine (TARC), peripheral eosinophil counts, lactate dehydrogenase serum levels (LDH), and total immunoglobulin E serum levels (IgE). TARC serum levels (normal, < 450 pg/mL for adults) are related to AD severity [17]. The eosinophils in the peripheral blood (normal, 70–450/μL) are useful in estimating AD severity [18]. LDH serum levels (normal, 105–245 IU/L) are a useful parameter of AD severity in the short term [18]. Total IgE levels in serum (normal, < 170 IU/mL) are an indicator of the long-term response to the AD treatment [19‐21]. Tension in the cervical muscle was assessed by measuring the cervical ROM using radiography, with higher scores indicating more flexibility and mobility and less stiffness [22].

Patient-reported outcomes regarding the psychological burden included the Hospital Anxiety and Depression Scale (HADS), VAS for sleep disturbance, Pittsburgh Sleep Quality Index (PSQI), Dermatology Life Quality Index (DLQI), and Short Form-36 Health Survey (SF-36v2). HADS screens for symptoms of anxiety and depression. It is scored on a scale of 0–21 for each subscale; a score ≤ 7 is normal, a score of 8–10 is considered borderline, and a score ≥ 11 indicates clinically significant anxiety or depression [23]. The VAS score for sleep disturbance ranges from 0 to 100, with higher scores indicating no sleep at all [24]. PSQI sets a range from 0 to 21, with higher scores indicating more sleep disturbance [25]. The DLQI has a range of 0–30, and higher scores are associated with a lower quality of life (QoL) [26, 27] and an MCID change of 4 points [27]. The SF-36v2 score ranges from 0 to 100, with higher scores indicating a greater health-related QoL (HRQoL) [28].

Only nonmedicated emollients were applied topically during the study period, and emollients with antioxidant or anti-inflammatory substances were not used. Topical medicated treatments [topical corticosteroids, calcineurin inhibitors, Janus kinase (JAK) inhibitors, antihistamines, antibiotic ointments, tars] and systemic treatments (oral corticosteroids, molecular-targeted drugs, or antiallergic medications) were not used.

This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments, and reviewed and approved by the local ethics review board in Tokyo (no. 635023-20181214). Documented informed consent was obtained from all patients.

Overall, 21 patients participated in this study, and 20 completed the treatment (Table 2). One patient experienced an exacerbation, was hospitalized, and withdrew from the study owing to psychological stress caused by a natural disaster. The mean overall duration of treatment was 76 (42–133) days.

The VAS score for pruritus decreased significantly after the treatment (Table 3 and Fig. 1a). The total POEM and 5-D itch scores improved significantly compared with the respective pretreatment scores (Table 3). Regarding itch frequency on POEM, all patients experienced pruritus daily during the week before the treatment, and 80% (16/20) of them described experiencing pruritus every day of the week after the treatment (Table 4). Regarding the duration of itch on the 5-D pruritus scale, 70% (14/20) of the patients experienced pruritus for at least 12 h per day before the treatment, and 15% (3/20) of patients reported pruritus for at least 12 h per day after the treatment. The degree of itch was graded as unbearable and severe on the 5-D pruritus scale by 30% (6/20) and 60% (12/20) of patients before the treatment, respectively; after the treatment, 0% and 30% (6/20) of patients reported their itch as unbearable and severe, respectively. Concerning improvement or worsening, 35% (7/20) and 50% (10/20) of patients reported that their symptoms worsened and remained unchanged before the treatment, respectively; after the treatment, 5% (1/20) each reported their symptoms were worsened and unchanged, respectively. Before the treatment, 15% (3/20) and 0% of patients reported that itching was slightly better but still present and much better but still present, respectively; after the treatment, 45% (9/20) of patients reported that itching was slightly better or much better but still present.

EASI, IGA, and BSA scores were significantly improved after the treatment (Table 3). In the EASI score, 95% (19/20) of patients reached EASI-50, 45% (9/20) reached EASI-75, and none reached EASI-90 (Table 5). A two-grade reduction of IGA score from the baseline was achieved by 40% (8/20) of the patients, and 5% (1/20) of patients had IGA scores of 0 (clear) or 1 (almost clear) after the treatment (data not shown).

The serum TARC and LDH levels, as well as the eosinophil count in the peripheral blood, were significantly improved after the treatment. However, the change in the serum total IgE levels did not achieve statistical significance (Table 3 and Fig. 2).

Cervical ROM, which is related to neck stiffness, was significantly improved. The average cervical ROM was 95.9° before the treatment and improved to 110.2° after the treatment (Table 3 and Fig. 1b).

The total HADS score decreased significantly after the treatment (Table 3). Before the treatment, 45% (9/20) of the patients had subscale scores of at least 11 for anxiety or depression, which is regarded as the threshold value in anxiety or depression clinical cases. The percentage of patients with anxiety or depression subscale scores of 11 or higher decreased to 30% (6/20) after the treatment (Table 6). The VAS score for sleep disturbance and the PSQI score, which strongly suggests sleep disturbance, significantly decreased after the treatment (Table 3 and Fig. 1c). The total DLQI score, which coincides with a significant impact on the patients’ daily lives, decreased significantly after the treatment (Table 3 and Fig. 1d).

Additionally, SF36v2 is a self-administered generic HRQoL questionnaire composed of 36 items related to eight domains and three summaries. It demonstrated significant improvements in the domains of role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH), and a mild change in physical functioning (PF) after the treatment (Table 7). The physical component summary (PCS) did not change, while the mental component summary (MCS) and role-social component summary (RCS) significantly improved (data not shown).