Case report
Etanercept in the treatment of SAPHO syndrome Luis-Carlos S aez-Martın1, MD, Susana G omez-Castro2, PhD, Concepci on Rom an-Curto3, 3 PhD, Irene Palacios-Alvarez , MD, and Emilia Fern andez-L opez3, PhD
1 Department of Dermatology, University General Hospital Gregorio Maran˜o´n of Madrid, Madrid, Spain, Departments of 2 Rheumatology, and 3Dermatology, University Hospital of Salamanca, Salamanca, Spain
Correspondence ez-Martın, MD Luis-Carlos Sa Department of Dermatology University General Hospital Gregorio Maran˜o´n Doctor Esquerdo 46 28007 Madrid (Madrid) Spain E-mail: [email protected] Conflicts of interest: None.
Introduction
e206
The acronym SAPHO was coined in 1987 to describe a rare syndrome with the following clinical characteristics: Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis.1–3 Skin manifestations are multiple: severe acne, palmoplantar pustulosis, hidradenitis suppurativa, or several psoriasis patterns.2–5 The most common form of articular manifestation is symmetrical and bilateral arthritis of the sternoclavicular joints.3 There are three diagnostic criteria: chronic recurrent multifocal osteomyelitis with or without dermatological manifestations; acute or chronic sterile arthritis associated with severe acne, pustular psoriasis, or palmoplantar pustulosis; and sterile osteitis in the presence of one of the skin manifestations.3,6 Both the dermatological and articular symptoms appear as outbreaks,2 and they can both occur simultaneously or separated by variable time intervals.2,3 The etiology of this syndrome is unknown.2,5 Some authors have stated that this arthropathy is due to a reaction to Propionibacterium acnes or other microorganisms that have low infectiveness in genetically predisposed patients, whereas other authors believe that it is attributed to a seronegative spondyloarthropathy.1–3,5,6 The analysis may show an increased level of acute phase reactants. HLA-B27 may be positive, while rheuInternational Journal of Dermatology 2015, 54, e206–e208
matoid factor and anti-CCP2 are negative. No autoantibodies have been found.1 SAPHO syndrome is associated with inflammatory cytokine release and global neutrophil activation.1 Tumor necrosis factor (TNF)-a productions could play a role in initiating inflammation and polymorphonuclear neutrophil infiltration in this patient group.1 The fact that elevated levels of TNF-a have been found in the biopsies of these patient’s articular bone have led to the treatment of refractory patients with anti-TNF-a drugs.2,5 Report The patient is a 39-year-old woman with no family history of psoriasis who presents with palmoplantar pustulosis and pustular psoriasis plaques on the legs and elbows of 14 years evolution (Fig. 1). The patient also presented arthritis in the sternocostoclavicular joints, spondyloarthropathy of the right sacroiliac joint, and osteitis in the base of the first distal phalanges of both feet. The osteoarticular manifestations appeared three years after the onset of the skin lesions (Fig. 2). The analysis revealed increased levels of acute phase reactants. Rheumatoid factor and HLA-B27 were negative. The skin manifestations and pattern of joint involvement allowed us to establish the clinical diagnosis of ª 2014 The International Society of Dermatology
ez-Martın et al. Sa
Etanercept and SAPHO syndrome
Case report
Figure 1 (a,b) Well-delineated erythematous plaques with pustular component yellowish scabs on elbows and leg. (c) On the soles of both feet we can see, over the normal or erythematous skin, deep pustules that partially converge on lakes of pus
Figure 2 (a) Simple x-ray of sacroiliac joints: right sacroilitis grade I–II with signs of bone reparation (bone bridge) on the upper third. (b) Simple x-ray of both feet: bone proliferation on the base of the first distal phalanges (more pronounced on the right side)
SAPHO syndrome. The laboratory tests also helped in the differential diagnosis. The skin lesions were refractory to several topical treatments: corticoids, salicylic acid, calcipotriol, tacalcitol, or tazarotene. Systemic therapies, such as psoralen + ultraviolet A, methotrexate, acitretin, and leflunomide had to be suspended due to the appearance of complications and/or little improvement of skin and articular lesions. We decided to treat our patient with etanercept 50 mg twice a week for the first 12 weeks and then 50 mg once a week. The lesions improved satisfactorily from the first month of treatment and with no side effects during the treatment (Fig. 3). The Dermatology Life Quality Index, which in the pretreatment stage had a score of 20, showed a score of 0 after treatment. The articular involvement also showed a favorable progress at the same time. Discussion In the treatment of pustular lesions of SAPHO syndrome, the main approach is the use of topical agents, such as ª 2014 The International Society of Dermatology
corticosteroids, retinoids, psoralen + ultraviolet A, and other agents such as dithranol, all of them with varying results.3 The treatment of osteoarticular symptoms is based on nonsteroidal anti-inflammatory drugs. The second line of treatment consists of classic systemic therapies with corticoids, retinoids, or disease-modifying antirheumatic drugs with very uneven results.2,3,5 Other drugs have also been used such as tetracyclines or bisphosphonates.6 The arrival of the era of biological drugs has considerably improved the treatment of refractory SAPHO syndrome.1,2,7–9 These findings increase the complexity of understanding the etiopathogenesis of this disease and its relation with classic plaque psoriasis, as the use of antiTNF have triggered some paradoxical cases of palmoplantar pustulosis.8,10 There are currently few cases published in the literature of patients with SAPHO syndrome who were successfully treated with etanercept.1,2,4,5,7 Etanercept therapy downregulated polymorphonuclear neutrophil functions and cytokine production, in line with the clinical effectiveness of this TNF-a antagonist, International Journal of Dermatology 2015, 54, e206–e208
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Case report
ez-Martın et al. Sa
Etanercept and SAPHO syndrome
Figure 3 (a,b) Residual leukoderma on elbows and feet, 12 weeks after treatment with etanercept. (c) Both soles reveal erythema, discrete desquamation and residual scabs with no evidence of pustules
preventing the interaction of TNF with its receptors on immune effector cells to bind competitively and reversibly both circulating TNF and the membrane bound TNF.1 Our case allows us to confirm that etanercept is a satisfactory therapeutic option for cases of SAPHO syndrome in which other systemic treatments have failed or are contraindicated. These results match the data extracted from the literature, although more studies and clinical essays are required to confirm these results.
5
6
7
References 1 Hurtado-Nedelec M, Chollet-Martin S, Nicaise-Roland P, et al. Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Rheumatology (Oxford) 2008; 47: 1160– 1167. 2 Moll C, Hern andez MV, Ca~ nete JD, et al. Ilium osteitis as the main manifestation of the SAPHO syndrome: response to infliximab therapy and review of the literature. Semin Arthritis Rheum 2008; 37: 299–306. 3 Zhao Z, Li Y, Li Y, et al. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with review of the relevant published work. J Dermatol 2011; 38: 155–159. 4 Coloe J, Diamantis S, Henderson F, et al. Synovitis-acnepustulosis-hyperostosis-osteitis (SAPHO) syndrome
International Journal of Dermatology 2015, 54, e206–e208
8
9
10
complicated by seven pulmonary emboli in a 15-year old patient. J Am Acad Dermatol 2010; 62: 333–336. Wagner AD, Andresen J, Jendro MC, et al. Sustained response to tumor necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum 2002; 46: 1965–1968. Vilar-Alejo J, Dehesa L, de la Rosa-del Rey P, et al. SAPHO syndrome with unusual cutaneous manifestations treated successfully with etanercept. Acta Derm Venereol 2010; 90: 531–532. Senabre-Gallego JM, Rosas-G omez de Salazar J, SantosSoler G, et al. Duration of treatment with etanercept and motives for discontinuation in a cohort of patients with rheumatic disease. Reumatol Clin 2011; 7: 385–388. Ben Abdelghani K, Dran DG, Gottenberg JE, et al. Tumor necrosis factor-alpha blockers in SAPHO syndrome. J Rheumatol 2010; 37: 1699–1704. Garcovich S, Amelia R, Magarelli N, et al. Long-term treatment of severe SAPHO syndrome with adalimumab: case report and a review of the literature. Am J Clin Dermatol 2012; 13: 55–59. Wollina U, Hansel G, Koch A, et al. Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients. Am J Clin Dermatol 2008; 9: 347.
ª 2014 The International Society of Dermatology
Etanercept in the treatment of SAPHO syndrome Luis-Carlos S aez-Martın1, MD, Susana G omez-Castro2, PhD, Concepci on Rom an-Curto3, 3 PhD, Irene Palacios-Alvarez , MD, and Emilia Fern andez-L opez3, PhD
1 Department of Dermatology, University General Hospital Gregorio Maran˜o´n of Madrid, Madrid, Spain, Departments of 2 Rheumatology, and 3Dermatology, University Hospital of Salamanca, Salamanca, Spain
Correspondence ez-Martın, MD Luis-Carlos Sa Department of Dermatology University General Hospital Gregorio Maran˜o´n Doctor Esquerdo 46 28007 Madrid (Madrid) Spain E-mail: [email protected] Conflicts of interest: None.
Introduction
e206
The acronym SAPHO was coined in 1987 to describe a rare syndrome with the following clinical characteristics: Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis.1–3 Skin manifestations are multiple: severe acne, palmoplantar pustulosis, hidradenitis suppurativa, or several psoriasis patterns.2–5 The most common form of articular manifestation is symmetrical and bilateral arthritis of the sternoclavicular joints.3 There are three diagnostic criteria: chronic recurrent multifocal osteomyelitis with or without dermatological manifestations; acute or chronic sterile arthritis associated with severe acne, pustular psoriasis, or palmoplantar pustulosis; and sterile osteitis in the presence of one of the skin manifestations.3,6 Both the dermatological and articular symptoms appear as outbreaks,2 and they can both occur simultaneously or separated by variable time intervals.2,3 The etiology of this syndrome is unknown.2,5 Some authors have stated that this arthropathy is due to a reaction to Propionibacterium acnes or other microorganisms that have low infectiveness in genetically predisposed patients, whereas other authors believe that it is attributed to a seronegative spondyloarthropathy.1–3,5,6 The analysis may show an increased level of acute phase reactants. HLA-B27 may be positive, while rheuInternational Journal of Dermatology 2015, 54, e206–e208
matoid factor and anti-CCP2 are negative. No autoantibodies have been found.1 SAPHO syndrome is associated with inflammatory cytokine release and global neutrophil activation.1 Tumor necrosis factor (TNF)-a productions could play a role in initiating inflammation and polymorphonuclear neutrophil infiltration in this patient group.1 The fact that elevated levels of TNF-a have been found in the biopsies of these patient’s articular bone have led to the treatment of refractory patients with anti-TNF-a drugs.2,5 Report The patient is a 39-year-old woman with no family history of psoriasis who presents with palmoplantar pustulosis and pustular psoriasis plaques on the legs and elbows of 14 years evolution (Fig. 1). The patient also presented arthritis in the sternocostoclavicular joints, spondyloarthropathy of the right sacroiliac joint, and osteitis in the base of the first distal phalanges of both feet. The osteoarticular manifestations appeared three years after the onset of the skin lesions (Fig. 2). The analysis revealed increased levels of acute phase reactants. Rheumatoid factor and HLA-B27 were negative. The skin manifestations and pattern of joint involvement allowed us to establish the clinical diagnosis of ª 2014 The International Society of Dermatology
ez-Martın et al. Sa
Etanercept and SAPHO syndrome
Case report
Figure 1 (a,b) Well-delineated erythematous plaques with pustular component yellowish scabs on elbows and leg. (c) On the soles of both feet we can see, over the normal or erythematous skin, deep pustules that partially converge on lakes of pus
Figure 2 (a) Simple x-ray of sacroiliac joints: right sacroilitis grade I–II with signs of bone reparation (bone bridge) on the upper third. (b) Simple x-ray of both feet: bone proliferation on the base of the first distal phalanges (more pronounced on the right side)
SAPHO syndrome. The laboratory tests also helped in the differential diagnosis. The skin lesions were refractory to several topical treatments: corticoids, salicylic acid, calcipotriol, tacalcitol, or tazarotene. Systemic therapies, such as psoralen + ultraviolet A, methotrexate, acitretin, and leflunomide had to be suspended due to the appearance of complications and/or little improvement of skin and articular lesions. We decided to treat our patient with etanercept 50 mg twice a week for the first 12 weeks and then 50 mg once a week. The lesions improved satisfactorily from the first month of treatment and with no side effects during the treatment (Fig. 3). The Dermatology Life Quality Index, which in the pretreatment stage had a score of 20, showed a score of 0 after treatment. The articular involvement also showed a favorable progress at the same time. Discussion In the treatment of pustular lesions of SAPHO syndrome, the main approach is the use of topical agents, such as ª 2014 The International Society of Dermatology
corticosteroids, retinoids, psoralen + ultraviolet A, and other agents such as dithranol, all of them with varying results.3 The treatment of osteoarticular symptoms is based on nonsteroidal anti-inflammatory drugs. The second line of treatment consists of classic systemic therapies with corticoids, retinoids, or disease-modifying antirheumatic drugs with very uneven results.2,3,5 Other drugs have also been used such as tetracyclines or bisphosphonates.6 The arrival of the era of biological drugs has considerably improved the treatment of refractory SAPHO syndrome.1,2,7–9 These findings increase the complexity of understanding the etiopathogenesis of this disease and its relation with classic plaque psoriasis, as the use of antiTNF have triggered some paradoxical cases of palmoplantar pustulosis.8,10 There are currently few cases published in the literature of patients with SAPHO syndrome who were successfully treated with etanercept.1,2,4,5,7 Etanercept therapy downregulated polymorphonuclear neutrophil functions and cytokine production, in line with the clinical effectiveness of this TNF-a antagonist, International Journal of Dermatology 2015, 54, e206–e208
e207
e208
Case report
ez-Martın et al. Sa
Etanercept and SAPHO syndrome
Figure 3 (a,b) Residual leukoderma on elbows and feet, 12 weeks after treatment with etanercept. (c) Both soles reveal erythema, discrete desquamation and residual scabs with no evidence of pustules
preventing the interaction of TNF with its receptors on immune effector cells to bind competitively and reversibly both circulating TNF and the membrane bound TNF.1 Our case allows us to confirm that etanercept is a satisfactory therapeutic option for cases of SAPHO syndrome in which other systemic treatments have failed or are contraindicated. These results match the data extracted from the literature, although more studies and clinical essays are required to confirm these results.
5
6
7
References 1 Hurtado-Nedelec M, Chollet-Martin S, Nicaise-Roland P, et al. Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Rheumatology (Oxford) 2008; 47: 1160– 1167. 2 Moll C, Hern andez MV, Ca~ nete JD, et al. Ilium osteitis as the main manifestation of the SAPHO syndrome: response to infliximab therapy and review of the literature. Semin Arthritis Rheum 2008; 37: 299–306. 3 Zhao Z, Li Y, Li Y, et al. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with review of the relevant published work. J Dermatol 2011; 38: 155–159. 4 Coloe J, Diamantis S, Henderson F, et al. Synovitis-acnepustulosis-hyperostosis-osteitis (SAPHO) syndrome
International Journal of Dermatology 2015, 54, e206–e208
8
9
10
complicated by seven pulmonary emboli in a 15-year old patient. J Am Acad Dermatol 2010; 62: 333–336. Wagner AD, Andresen J, Jendro MC, et al. Sustained response to tumor necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum 2002; 46: 1965–1968. Vilar-Alejo J, Dehesa L, de la Rosa-del Rey P, et al. SAPHO syndrome with unusual cutaneous manifestations treated successfully with etanercept. Acta Derm Venereol 2010; 90: 531–532. Senabre-Gallego JM, Rosas-G omez de Salazar J, SantosSoler G, et al. Duration of treatment with etanercept and motives for discontinuation in a cohort of patients with rheumatic disease. Reumatol Clin 2011; 7: 385–388. Ben Abdelghani K, Dran DG, Gottenberg JE, et al. Tumor necrosis factor-alpha blockers in SAPHO syndrome. J Rheumatol 2010; 37: 1699–1704. Garcovich S, Amelia R, Magarelli N, et al. Long-term treatment of severe SAPHO syndrome with adalimumab: case report and a review of the literature. Am J Clin Dermatol 2012; 13: 55–59. Wollina U, Hansel G, Koch A, et al. Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients. Am J Clin Dermatol 2008; 9: 347.
ª 2014 The International Society of Dermatology
