Isotretinoin-induced inflammatory back pain and sacroiliitis in patients with moderate-to-severe acne vulgaris.

INTRODUCTION: Isotretinoin has been reported to induce inflammatory back pain (IBP) and sacroiliitis in the patients with acne vulgaris. The aim of this study is to investigate the incidence of IBP and sacroiliitis in patients receiving isotretinoin treatment compared with oral antibiotics for acne vulgaris. MATERIALS AND METHODS: A total of 201 patients with moderate-to-severe acne vulgaris who received isotretinoin (n = 100) or oral antibiotics (n = 101) were included in the study. All patients were monthly questioned for IBP symptoms during their treatment. Patients described IBP were also evaluated for sacroiliitis by c-reactive protein, sedimentation rate, HLAB27, and sacroiliac magnetic resonance imaging (MRI). Isotretinoin was discontinued in all patients diagnosed as sacroiliitis, and these patients were reevaluated after 3 months. RESULTS: IBP was observed in 21 (10.4%), and sacroiliitis was detected in 11 (11%) patients on isotretinoin treatment; in oral antibiotic group, we did not observe IBP or sacroiliitis. The incidence of IBP and sacroiliitis differed significantly between the isotretinoin and oral antibiotic groups (p < 0.0001, p = 0.02). Complete regression was observed in the great majority of patients following cessation of isotretinoin. CONCLUSIONS: Our study is the largest prospective controlled study that investigated the incidence of sacroiliitis in patients receiving isotretinoin and compared with patients using oral antibiotics.

Two pediatric cases of isotretinoin-induced sacroiliitis successfully treated with adalimumab.

Isotretinoin is widely used in severe acne. Isotretinoin has many side effects. Sacroiliitis is one of these side effects and has been rarely reported in the children. Herein, we present two children with isotretinoin-induced sacroiliitis resistant to anti-rheumatic drugs and successfully treated with adalimumab.

A patient with chronic sacroiliitis undiagnosed for three years after isotretinoin use.

BACKGROUND: Isotretinoin (ISO) is a synthetic vitamin A derivative which has been used for treatment-resistant acne vulgaris. Although most musculoskeletal side effects of ISO are common, including myalgia, arthralgia, and back pain, sacroiliitis is one of the uncommon side effects. ISO-induced sacroiliitis usually completely resolves within a few months by the cessation of the drug. CASE PRESENTATION: In this paper, we present a 26-year-old female patient with chronic sacroiliitis that was probably induced by ISO and not resolved by the discontinuation of the drug. CONCLUSION: In this patient, sacroiliitis was overlooked for three years. Therefore, ISO usage should be considered in the differential diagnosis of sacroiliitis and low back pain.

New onset of axial spondyloarthropathy in patients treated with isotretinoin for acne vulgaris: incidence, follow-up, and MRI findings.

INTRODUCTION: Oral isotretinoin is commonly prescribed for acne vulgaris. Several case reports and observational studies have reported serious musculoskeletal side effects; however, the incidence, imaging findings, and longitudinal follow-up data are limited for patients who develop inflammatory back pain (IBP). OBJECTIVE: To assess the incidence of isotretinoin-triggered axial spondyloarthropathy (SpA) in acne vulgaris patients based on clinical features and MRI findings and to examine clinical and radiological outcomes following drug withdrawal. METHODS: Five hundred thirteen acne patients receiving isotretinoin were screened for IBP; IBP patients were assessed for CRP, plain radiographs, and MRI of the sacroiliac joint. MRI-proven sacroiliitis was scored semi-quantitatively. Patients were followed longitudinally to assess SpA clinical course and longitudinal MRI sacroiliac joints, and CRP levels were reassessed 3 weeks after patients were symptom-free, following isotretinoin discontinuation. RESULTS: Of the 513 patients, 23.98% developed IBP. MRI-proven sacroiliitis was detected in 42.3% of the symptomatic patients or 10.1% of the cohort. Among MRI-proven sacroiliitis cases, 51.9% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA. Mean CRP level was 32.05 ± 17.23 mg/L at pain onset and 3.4 ± 2.7 mg/L after symptom resolution. MRI findings completely resolved within 9 months (mean 6.27 ± 1.7) after isotretinoin discontinuation. MRI scores positively correlated with baseline CRP levels and global acne grading system score, pain, and the Ankylosing Spondylitis Disease Activity Score. CONCLUSION: Isotretinoin-induced axial SpA is a prevalent side effect in acne vulgaris patients. Early detection and follow-up of isotretinoin-induced sacroiliitis can be facilitated by MRI. Cessation of isotretinoin resulted in complete resolution in all affected patients.Key Points• Detection of underdiagnosed isotretinoin side effects which are common but not always correctly diagnosed and managed.• Incidence, diagnosis, and management of these side effects in a real-world setting.• This is the first large prospective longitudinal cohort study to report on axial manifestations in patients treated with isotretinoin as well as the effect of drug cessation upon the clinical, laboratory, and radiological findings.

Effect of Serum 25 Hydroxy Vitamin D Level on Isotretinoin-Induced Musculoskeletal Symptoms: A Cross-Sectional Study.

Isotretinoin (ISO) is a drug which is used for the treatment of severe and refractory acne vulgaris (AV), over the last few decades. The drug has various musculoskeletal side effects. The aim of this study was to investigate relationship between serum 25 hydroxy (OH) vitamin D levels and the ISO-induced musculoskeletal side effects in patients with AV. We included 87 patients receiving ISO and had musculoskeletal symptoms as adverse effect (AE) group. Another 90 patients receiving ISO for AV and had any musculoskeletal complaints were recruited as control (C) group. Locomotor system examination of the patients was performed by the same clinician. Serum 25 OH vitamin D levels of the all participants were measured. Patients in the AE group were divided into three subgroups by serum 25 OH vitamin D levels. Patients with serum 25 OH vitamin D level lower than 10 ng/ml was classified as Group I, the ones between 10-20 ng/ml as Group II and those higher than 20 ng/ml were classified as Group III. AE and C groups were similar in terms of age and sex (p > 0.05). There was no statistically significant difference in the mean serum vitamin D levels between two groups (p = 0.17). Also, there was no significant difference in number of arthralgia (p = 0.30), myalgia (p = 0.29), low back pain (p = 0.10) and sacroiliitis (p = 0.17) between three subgroups in AE group. In addition, we found no statistically significant correlation between the serum vitamin D levels and age, cumulative dose of ISO, arthralgia, myalgia and sacroiliitis parameters in AE group (p > 0.05). Serum 25 OH vitamin D levels between the AE and C groups were similar. We also found that no significant difference in musculoskeletal adverse events between AE subgroups. Therefore, it can be concluded that vitamin D deficiency has no effect on the musculoskeletal adverse events in patients receiving ISO.

Isotretinoin-induced sacroiliitis: Case series of four patients and a systematic review of the literature.

Isotretinoin is the mainstay treatment in severe acne; however, its musculoskeletal adverse effects such as lower-back pain can be disabling. Herein, we present four cases of isotretinoin-induced sacroiliitis with variable severity. We also present a review of the literature of isotretinoin-induced sacroiliitis. All our cases were male and human leukocyte antigen (HLA)-B27 negative. Sacroiliitis was detected a median of 55 (10-120) days after isotretinoin initiation. Two patients were responsive to baseline sulfasalazine and indomethacin treatment, while the other two patients required more intensive treatments: adalimumab in one and methotrexate in the other. We also identified 15 articles describing 33 patients (17 of whom were female) with isotretinoin-induced sacroiliitis. Most of them were responsive to low-to-medium doses of systemic steroids or non-steroidal anti-inflammatory drugs (NSAIDs). Our patients illustrate that severity of isotretinoin-induced sacroiliitis varies from patient to patient.

Isotretinoin-induced sacroiliitis in patients with hidradenitis suppurativa: a case-based review.

Hidradenitis suppurativa (HS) is a chronic, suppurative skin disease characterized by painful nodules, particularly in the axillae and groin. Isotretinoin can be used in the treatment of HS; however, it may paradoxically lead to skin lesions or worsen the existing lesions. Isotretinoin, which is commonly used in the treatment of severe acne, is associated with several side effects, including rheumatic side effects and rarely sacroiliitis. In this study, we discussed two cases who presented with low back pain after isotretinoin was used for the treatment of acne vulgaris. The patients did not have low back pain before isotretinoin use and did not have enthesitis, dactylitis, uveitis, psoriasis, recent infection, trauma, and family history spondylitis. HLA-B27 was negative. Bone-marrow edema was detected at the sacroiliac joint on magnetic resonance imaging. Because of these findings, sacroiliitis related to the drug was considered in our patients and isotretinoin treatments were discontinued. Because the patients' low back pain continued when they administered non-steroidal anti-inflammatory drugs, biological drug treatments were started. Both cases presented had a simultaneous HS lesion. After the treatment, both low back pain and HS lesions regressed. Patients with isotretinoin therapy should be alerted for inflammatory low back pain and HS lesions that may develop. We should note that biologic agents should be considered in the treatment of resistant cases.

Emergence of severe spondyloarthropathy-related entheseal pathology following successful vedolizumab therapy for inflammatory bowel disease.

OBJECTIVES: Vedolizumab (VDZ) blocks α4ß7 integrin and is licenced for the treatment of IBD. It has been associated with mild SpA-related features, including sacroiliitis and synovitis. Herein we report a series of cases demonstrating the emergence of severe SpA-associated enthesitis/osteitis following successful IBD therapy with VDZ. METHODS: We evaluated 11 VDZ-treated patients with IBD across seven centres who developed severe active SpA and/or enthesopathy, with the aim of characterizing the VDZ-associated SpA or entheseal flares. Imaging features demonstrating particularly severe disease were recorded. RESULTS: De novo SpA developed in 9 of 11 patients and flare of known SpA in 2 patients, with 4 patients requiring hospitalization due to disease severity. Available data showed that one of seven cases were HLA-B27 positive. The median time from VDZ initiation to flare was 12 weeks, with IBD well controlled in 7 of 10 patients (no data for 1 patient) at flare. Severe SpA enthesitis/osteitis was evident on MRI or US, including acute sacroiliitis (n = 5), extensive vertebral osteitis (n = 1), peri-facetal oedema (n = 1) and isolated peripheral enthesitis (n = 3). Due to arthritis severity, VDZ was discontinued in 9 of 11 patients and a change in therapy, including alternative anti-TNF, was initiated. CONCLUSION: Severe SpA, predominantly HLA-B27 negative, with osteitis/enthesitis may occur under successful VDZ treatment for IBD, including in subjects with prior anti-TNF therapy for intestinal disease.

An induction or flare of arthritis and/or sacroiliitis by vedolizumab in inflammatory bowel disease: a case series.

BACKGROUND: In inflammatory bowel disease (IBD), a new biological therapy has recently been approved. Vedolizumab is a humanised IgG1 monoclonal antibody to α4ß7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4ß7-mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4ß7 integrin in the joint, led to the expectation of a therapeutic efficacy in spondyloarthritis. Nonetheless, the effect of vedolizumab on extraintestinal manifestations-and especially the joint-has not been reported so far. CASE REPORT: A series of five patients with IBD who were treated with vedolizumab and promptly developed new onset or exacerbation of sacroiliitis or arthritis are reported. CONCLUSIONS: Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism.

The prevalence of sacroiliitis in patients with acne vulgaris using isotretinoin.

BACKGROUND/OBJECTIVE: Acne vulgaris is a chronic inflammatory disease affecting the pilosebaceous unit in the skin. Isotretinoin is a synthetic vitamin A derivative regarded as the most effective agent in the treatment of acne. There have recently been increasing reports of adverse effects of isotretinoin on the skeletal system. Our aim in this study was to evaluate the rheumatic side-effects triggered by this drug, and particularly the prevalence of sacroiliitis. MATERIALS AND METHODS: A total of 73 patients receiving isotretinoin due to moderate or severe acne vulgaris were included. All patients were questioned about inflammatory low back pain and musculoskeletal pains during the treatment process. Inflammatory low back pain was evaluated using Assessment of Spondyloarthritis International Society (ASAS) criteria. Patients meeting ASAS criteria were evaluated with radiography and when necessary with sacroiliac magnetic resonance. RESULTS: The dose range for isotretinoin was between 0.4 and 0.8 mg/kg/day (mean 0.53 mg/kg/day). Treatment lasted for 6-8 months (mean 6.8 months). Lethargy was determined in 37 (50.7%) patients, myalgia in 31 (42.5%) and low back pain in 36 (49.3%). Mechanical low back pain symptoms were present in 20 of the patients describing low back pain and inflammatory low back pain in 16. Acute sacroiliitis was determined in six patients (8.2%) following a sacroiliac magnetic resonance imaging (MRI). Five (83.3%) of the patients with sacroiliitis were female and one (16.7%) was male. No statistically significant difference was determined between male and female patients in terms of prevalence of sacroiliitis (p = 0.392). CONCLUSION: The incidence of sacroiliitis in patients using isotretinoin is quite high. Patients using isotretinoin must be questioned about sacroiliitis findings and must be subjected to advanced assessment when necessary. Further studies regarding the development of sacroiliitis under isotretinoin therapy are now needed.

Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthritis.

Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of isotretinoin is transient muscle and/or joint pains. Here, we report a case with bilateral wrist and metacarpophalangeal joint arthritis and unilateral sacroiliitis associated with isotretinoin usage to attract attention, particularly from physiatrists, rheumatologists and dermatologists, to this rare adverse effect of isotretinoin.

Sacroiliitis after use of oral isotretinoin--association with acne fulminans or adverse effect?

Acne fulminans is a rare and severe form of acne that may evolve from acne vulgaris, especially in male adolescents, or occur as an adverse effect of oral isotretinoin. Arthritis is a serious clinical manifestation when the musculoskeletal system is compromised by AF and has been reported as a rare adverse effect of isotretinoin. Involvement of the sacroiliac joints occurs in 21% of acne fulminans cases. We present the case of a 18-year-old male patient in whom acne fulminans evolved from acne vulgaris grade IV and after inflammation resolution started treatment with oral isotretinoin. Within a 30-day period of retinoid treatment he presented with back pain followed by rapid, progressive inability to deambulate.

Sacroiliitis after use of oral isotretinoin - association with acne fulminans or adverse effect? / Sacroileite apos uso de isotretinoina oral - associacao com acne fulminans ou efeito adverso?

Acne fulminans is a rare and severe form of acne that may evolve from acne vulgaris, especially in male adolescents, or occur as an adverse effect of oral isotretinoin. Arthritis is a serious clinical manifestation when the musculoskeletal system is compromised by AF and has been reported as a rare adverse effect of isotretinoin. Involvement of the sacroiliac joints occurs in 21% of acne fulminans cases. We present the case of a 18-year-old male patient in whom acne fulminans evolved from acne vulgaris grade IV and after inflammation resolution started treatment with oral isotretinoin. Within a 30-day period of retinoid treatment he presented with back pain followed by rapid, progressive inability to deambulate.

Acne fulminans é uma forma grave e rara de acne que pode ser evolução da acne vulgar, principalmente em adolescentes do sexo masculino, ou ser precipitada durante o tratamento com isotretinoína oral. A artrite pode ocorrer como grave complicação na acne fulminans e já foi relatada como efeito adverso raro da isotretinoína. O acometimento das articulações sacroilíacas ocorre em 21% das artrites associadas à acne fulminans. Relatase caso de paciente masculino, 18 anos, que desenvolveu acne fulminans a partir de acne vulgar grau IV/conglobata e após resolução do quadro inflamatório, foi iniciado tratamento da acne com isotretinoína. Com 30 dias de uso do retinóide, o paciente iniciou dor lombar com piora rápida, progressiva que o incapacitou de deambular.

Sacroiliitis secondary to isotretinoin.

Reported is the case of a 17-year old male with sacroiliitis confirmed by magnetic resonance imaging (MRI) while undergoing isotretinoin treatment for acne vulgaris. The cessation of isotretinoin and symptomatic treatment resolved the symptoms within 6 weeks, with no signs of sacroiliitis on repeat MRI 10 months later. The temporal association of disease onset and commencement of isotretinoin along with rapid recovery on withdrawal supports the role of isotretinoin in this case.