SAPHO Syndrome Presenting With Severe Inflammatory Back Pain (Sacroiliitis) and Rare Retinol Associated Myopathy in an Iraqi Adolescent Male: A Case Report and Literature Review Authors: Farah Jaafar Mahdi, Ali Saad Al‐Shammari, Mustafa Majid Hameed, Marwah Sami Ahmed, Ibrahim Khalil, Zahraa Saeed Fahad, Ahmed Dahham Hasan, Nizar Abdulateef Jassim Published: 2026 ABSTRACT ABSTRACTSAPHO syndrome is a rare autoinflammatory disorder characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis. Although musculoskeletal and dermatologic manifestations are well recognized, extra‐articular involvement remains uncommon, particularly muscular inflammation. We report the case of a 17‐year‐old male who presented with severe inflammatory low back pain and extensive nodulocystic acne for which he took escalating doses of isotretinoin. Clinical examination demonstrated positive sacroiliac stress tests, proximal muscle myopathy, and dermatologic evaluation confirmed acne conglobata. Laboratory testing revealed markedly elevated inflammatory markers. Magnetic resonance imaging of the sacroiliac joints showed bilateral asymmetric active sacroiliitis, fulfilling clinical criteria for Axial Spondyloarthritis. The infectious and autoimmune workup was negative. The patient responded favorably to isotretinoin withdrawal and immunosuppressive therapy, with sustained remission following steroid withdrawal. This case describes a rare and severe isotretinoin‐associated inflammatory myopathy in SAPHO syndrome, highlighting the need to expand the differential diagnosis of myopathy in SAPHO syndrome. It is imperative to exercise caution when prescribing isotretinoin to patients with SAPHO syndrome. Introduction SAPHO syndrome (Synovitis, Arthritis, Pustulosis, Hyperostosis, Osteitis) is a rare disease, first described in 1987, characterized by a heterogeneous spectrum of manifestations, being considered an autoinflammatory condition as characterized by osteoarticular inflammation and inflammatory skin lesions. SAPHO is multifactorial in etiology, as it combines genetic, infectious, and immunological factors [1]. Criteria for diagnosis of SAPHO syndrome relies mainly on modified Khan criteria as shown in Table 1 [2]. TABLE 1Modified Khan criteria.CategoryCriteriaInclusionBone ± joint involvement associated with Palmoplantar Pustulosis and Psoriasis VulgarisBone ± joint involvement associated with severe acneIsolated sterile hyperostosis/osteitis (adults)Chronic recurrent multifocal osteomyelitis (children)Bone ± joint involvement associated with chronic bowel diseasesExclusionInfectious osteitisTumoral conditions of boneNon‐inflammatory condensing lesions of bone Modified Khan criteria. The syndrome usually affects patients with average ages of 30 and 50 years, although pediatric cases are also involved. Arthritis affects the majority of patients (about 92%) with more preference to the axial skeleton than peripheral joints (sacroiliac joints, spine, and enthesitis). Skin lesions in affected patients include palmoplantar pustulosis and severe acne (Acne conglobata, acne fulminans, or hidradenitis suppurativa (HS)) [3]. Treatment include combination of non‐steroidal anti‐inflammatory drugs (NSAIDS), corticosteroids, disease modifying anti‐rheumatic drugs (DMARDs) and biologic treatments. NSAIDs are usually considered first line and are the primary treatment. Steroid are typically used for short periods. The DMARDs like methotrexate are used effectively for peripheral arthritis and dermatological manifestations. Biologic treatments are effective and are used mainly in refractory cases [4]. Retinoids are the main pharmacologic therapy for many dermatologic diseases including severe acne. They are considered safe and effective. Arthralgia is a known side effect of this group, myalgia and polyneuropathy but more rarely, sacroiliitis can occur as musculoskeletal manifestations. Retinoids modulate key cellular pathways, particularly apoptosis and immune regulation and have been shown to induce Matrix metalloproteinase‐2 (MMP‐2) activity which is known to degrade type IV collagen in the basement membrane of epithelial cells of the joints. It is found more in arthritic joints [5, 6, 7]. Here, we present a unique adolescent case of SAPHO syndrome associated with inflammatory myopathy. Case Presentation A 17‐year‐old previously healthy male presented with an 8‐month history of severe nodulocystic acne involving the back and the anterior chest to a lesser extent (Figure 1), with painful pustules and progressive scarring, for which he visited multiple dermatologists who prescribed an escalating dose of isotretinoin to a maximum of 160 mg (2 mg/kg, weight 75 Kg) daily. There was a lack of response despite the large dose over 8 weeks prior to presentation. During this period, he developed a gradual onset of progressive proximal muscle weakness of the lower more than the upper limbs interfering with daily activities such as getting up from a sitting position and performance of above‐the‐head activities at which point he was referred to the rheumatology outpatient clinic. Upon questioning, he had a long history of inflammatory back pain with morning stiffness of more than one hour, night pain and it was relieved by exercise and increased with rest. Physical examination revealed extensive nodular acne over the back and upper chest as well as grade 3 proximal lower limbs muscle weakness, with a lesser degree of involvement seen distally. Dermatologic consultation confirmed a diagnosis of acne conglobata/acne fulminans. Examination of the patient's back was suggestive of sacroiliitis in all four tests (FABER, lateral distraction and direct compression tests). Both parents' consent was taken before the management and data collection. Clinical photograph of the patient's back. Photograph showing extensive nodulocystic and inflammatory acne lesions over the upper and mid‐back, consistent with severe acne conglobata, a recognized dermatologic manifestation associated with SAPHO syndrome. Image obtained prior to initiation of systemic immunosuppressive therapy. Methods The myopathy was in the differential of isotretinoin induced versus rare SAPHO association. Subsequent blood tests were sent, and they revealed elevated inflammatory markers, including C‐reactive protein and erythrocyte sedimentation rate, with otherwise unremarkable hematologic, renal (creatinine and estimated glomerular filtration rate), hepatic workup. Elevated lactate dehydrogenase (LDH) and borderline creatinine phosphokinase levels were noted. Myoglobin levels were unavailable in local labs. Extensive infectious and autoimmune evaluations were negative. (Table 2) Electromyography (EMG) confirmed features of inflammatory myopathy. Pelvic x‐ray was normal. Magnetic resonance imaging of the sacroiliac joints demonstrated bilateral asymmetric active sacroiliitis with periarticular bone marrow edema on T2‐weighted STIR sequences, more pronounced on the sacral side of the right joint, fulfilling the Assessment of Spondyloarthritis International Society (ASAS) criteria of active sacroiliitis [8] (Figure 2). At that point, SAPHO with severe sacroiliitis has been confirmed. To note, the patient has refused the biopsy and could not afford the scintigraphy. TABLE 2Laboratory and imaging findings.Laboratory InvestigationsTestResultReference RangeCommentC‐reactive protein (CRP)37 mg/L< 5 mg/LMarkedly elevatedErythrocyte sedimentation rate (ESR)49 mm/h< 15 mm/hElevatedWhite blood cell count11.2 × 109/L4–11 × 109/LNeutrophil predominanceHemoglobinNormal—No anemiaPlateletsNormal——Creatine kinase (CK)Normal30–200 U/LNo myonecrosisLactate dehydrogenase (LDH)287 U/L135–225 U/LMild elevationAlkaline phosphatase (ALP)142 U/L40–130 U/LMild elevationRenal function testsNormal—Preserved renal functionLiver enzymesNormal——Thyroid function testsNormal——Autoimmune serologyNegative—No systemic autoimmune diseaseInfectious workupNegative—Excludes infectionNeurophysiology (EDX/EMG)StudyFindingInterpretationNerve conduction studiesNormalNo peripheral neuropathyNeedle EMGDiffuse symmetric proximal myopathic patternInflammatory myopathy‐like processMembrane instabilityAbsentNon‐necrotizingImaging FindingsModalityFindingImpressionMRI sacroiliac joints (STIR)Bilateral asymmetric bone marrow edema (right > left), max depth ~12.4 mmActive inflammatory sacroiliitis (ASAS positive)Pelvic X‐rayHyperostotic changesConsistent with SAPHO syndrome Laboratory and imaging findings. Magnetic resonance imaging of the sacroiliac joints. T2‐weighted short tau inversion recovery images show bilateral, asymmetric periarticular bone marrow edema, greater on the sacral side of the right joint (maximum depth 12.4 mm), consistent with active sacroiliitis. Mild joint space narrowing is present without erosions, sclerosis, effusion, synovial hypertrophy, fat metaplasia, or adjacent soft‐tissue abnormalities. Findings fulfill the Assessment of Spondyloarthritis International Society (ASAS) magnetic resonance imaging criteria for active sacroiliitis. Results and Outcomes The decision was to stop isotretinoin, start anti‐inflammatory dose of NSAIDS without immunosuppressants to differentiated between the two mentioned differential diagnoses. –After 2 weeks, the patients presented for follow up with total resolution of sacroiliitis features as well as muscle power, but still the lesions were extensive, at that point started high dose prednisolone (20 mg 1 × 2 with subsequent tapering) and methotrexate.–After 3 months: The patient follow‐up showed significant improvement of the skin lesions despite cutting off steroids after 3 weeks. –After 2 weeks, the patients presented for follow up with total resolution of sacroiliitis features as well as muscle power, but still the lesions were extensive, at that point started high dose prednisolone (20 mg 1 × 2 with subsequent tapering) and methotrexate. After 2 weeks, the patients presented for follow up with total resolution of sacroiliitis features as well as muscle power, but still the lesions were extensive, at that point started high dose prednisolone (20 mg 1 × 2 with subsequent tapering) and methotrexate. –After 3 months: The patient follow‐up showed significant improvement of the skin lesions despite cutting off steroids after 3 weeks. After 3 months: The patient follow‐up showed significant improvement of the skin lesions despite cutting off steroids after 3 weeks. As conclusion, this case exemplifies an uncommon presentation of SAPHO syndrome in an adolescent, exacerbated by inflammatory myopathy following the administration of isotretinoin for acne treatment. It is imperative to emphasize the cautious use of Isotretinoin in patients with SAPHO syndrome. Further research is warranted to ascertain the safety of Isotretinoin usage in SAPHO patients. Discussion SAPHO syndrome is a neutrophilic autoinflammatory disorder marked by dysregulated innate immunity and cytokine overactivation. Severe acne variants, particularly acne conglobata and fulminans, are linked to heightened systemic inflammation and aggressive disease. Proposed mechanisms of the pathophysiology of SAPHO include neutrophil‐mediated inflammation and cytokine dysregulation involving IL‐1, IL‐17, and TNF‐alpha [9]. These pathways are known to drive both the primary bone lesions in SAPHO and systemic inflammation. Most SAPHO literature focuses on the “classic” pentad of symptoms. However, reports of muscle involvement are sparse, often limited to localized myositis adjacent to sites of osteitis. In contrast, our patient had an additional inflammatory myopathic process as evident by the EMG study possibly due to preceding isotretinoin use. In this case report, isotretinoin likely induced myopathy, as the skin changes were already present prior to starting isotretinoin and being improved by cutting off the drug only supports this hypothesis. In Our case report, Isotretinoin likely induced myopathy only, rather than myopathy was SAPHO‐ associated, as the skin changes were already present prior to starting isotretinoin and being improved by cutting off the drug only support this hypothesis versus SAPHO‐associated myositis. Luzzati et al. reported a case of isotretinoin‐associated SAPHO in an adolescent who presented with sacroiliitis after a 10‐week treatment with isotretinoin. The condition responded favorably to TNF‐α inhibition, underscoring both potential triggers and the efficacy of biologics in refractory disease. Notably, this case was not associated with myopathy [10]. Our case responded dramatically with NSAIDs and immunosuppression. Many cases reported to respond to conventional anti‐inflammatory therapy, DMARDs, or biologic agents. Freira et al. [11], reported an adolescent male with acne conglobata and sacroiliac involvement who experienced improvement with standard immunomodulatory treatment. Concurrently, additional pediatric and young adult cases have demonstrated marked responses to TNF‐α blockade in severe osteoarticular‐dermatologic SAPHO [12, 13, 14]. Other new emerging agents may have a more consistent effect; Risankizumab, a human monoclonal antibody directed against IL‐23p19, shows dramatic rheumatologic and dermatologic improvement in some case reports [15]. Our 17‐year‐old patient presented with muscular and joint symptoms after 8 weeks of initiation of isotretinoin; similarly, Geller ASB et al. described a case of an 18‐year‐old male with a history of fulminant acne, treated well with topicals and an oral course of retinoids, but after 30 days, the patient developed bilateral sacroiliitis as well as polyarthritis. This case did not report evidence of myositis or other features of SAPHO [16]. Another case report presented a 17‐year‐old male with a history of use of 40 mg of isotretinoin for acne vulgaris. A few weeks later, he developed painful limbs and chest, limiting his activity. After 3 months, he developed an inflammatory syndrome with fever and prominent sacroiliitis. The symptoms resolved well to NSAIDs plus isotretinoin cessation, which is inconsistent with the usual treatment of SAPHO which requires immunosuppression. Although the patient had muscle pain, it was mild and was not the chief complaint of the patient. Creatinine kinase was normal, similar to our study [17]. Coskun BN reported two young age (20,27 year) females with isotretinoin induced sacroiliitis and Hidradenitis suppurativa. The first case had used isotretinoin for 6 months for cystic acne vulgaris. Despite the use of NSAIDs, the pain persists and only with infliximab, the pain was controlled. The second case presented with the same picture. Remission was induced by adalimumab for both musculoskeletal and skin lesions. This was inconsistent with our case in which NSAIDs was effective, although only with DMRADs and steroids, the skin lesions resolved. The two patients did not have SAPHO syndrome [18]. In a recent systematic review, isotretinoin‐induced back pain and myalgia emerged as notable musculoskeletal complications in a significant number of patients. Notably, the increasing cumulative dose was associated with an increased incidence of side effects [19]. In one study, a total of 73 patients receiving isotretinoin due to moderate or severe acne vulgaris were included. Myalgia was present in 31, and low back pain in 36, in whom 6 had sacroiliitis [20]. In a recent case report, isotretinoin‐induced proximal myopathy was diagnosed in a young patient who had been taking the medication. The symptoms resolved after discontinuing the medication [21]. The patient had been taking oral isotretinoin (10 mg, twice weekly) for moderate acne over 5 months. No corticosteroids or other immunosuppression were required. Also, there is a case report of recurrent myositis secondary to isotretinoin use, with different localized muscle groups affected at each time, with different increment levels in CPK level. The first attack occurred after 3 months of treatment for rosacea, with mainly proximal upper girdle muscle involvement and associated features of rhabdomyolysis, with dark colored urine requiring intensive care admission. The next episode occurred 1 year later, after 5 months of re‐intake of isotretinoin, with mainly lower limb involvement and minor CPK elevation [22]. To note, Creatinine kinase is elevated only in 51% of patients with myositis [23]. Author Contributions Farah Jaafar Mahdi: conceptualization, data curation, formal analysis, methodology, supervision, validation, writing – original draft. Ali Saad Al‐Shammari: conceptualization, formal analysis, funding acquisition, supervision, writing – original draft. Mustafa Majid Hameed: data curation, investigation, methodology, validation, writing – original draft. Marwah Sami Ahmed: data curation, investigation, resources, visualization, writing – original draft. Ibrahim Khalil: validation, visualization, writing – review and editing. Zahraa Saeed Fahad: conceptualization, formal analysis, writing – original draft. Ahmed Dahham Hasan: conceptualization, data curation, supervision, validation, writing – original draft, writing – review and editing. Nizar Abdulateef Jassim: conceptualization, data curation, supervision, writing – review and editing. Funding The authors have nothing to report. Ethics Statement Written informed consent was obtained from the patient for publication of this case report and any accompanying images. This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines. Consent Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy. Conflicts of Interest The authors declare no conflicts of interest.