Acne fulminans (AF) is a severe form of inflammatory

and ulcerated acne associated with fever, malaise, joint swellings

and polyarthralgia.1 Osteoarticular lesions are often described

and can be radiologically indistinguishable from those observed

in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO)

syndrome.2,3 SAPHO is an autoinflammatory disease characterized

by osteoarticular and cutaneous manifestations, the latter

including nodular and fulminans acne, hidradenitis suppurativa

and palmoplantar pustulosis.3 Thus, AF is considered part of the

SAPHO spectrum.

Barbareschi

Cassel

Colina

Firinu

Laasonen

Nast

Nguyen

Wendling

Zaba

English

Acne fulminans (AF) is a severe form of inflammatory
and ulcerated acne associated with fever, malaise, joint swellings
and polyarthralgia.1 Osteoarticular lesions are often described
and can be radiologically indistinguishable from those observed
in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO)
syndrome.2,3 SAPHO is an autoinflammatory disease characterized
by osteoarticular and cutaneous manifestations, the latter
including nodular and fulminans acne, hidradenitis suppurativa
and palmoplantar pustulosis.3 Thus, AF is considered part of the
SAPHO spectrum.

Teresa Oranges

Antonella Insalaco

A Diociaiuti

C Carnevale

Raffaele Strippoli

G. Zambruno

P. Toma

Maya El Hachem

Archivio della ricerca- Università di Roma La Sapienza

LETTER TO THE EDITORSevere osteoarticularinvolvement in isotretinoin-triggered acne fulminans: twocases successfully treated withanakinraEditorAcne fulminans (AF) is a severe form of inflammatoryand ulcerated acne associated with fever, malaise, joint swellingsand polyarthralgia.1 Osteoarticular lesions are often describedand can be radiologically indistinguishable from those observedin synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO)syndrome.2,3 SAPHO is an autoinflammatory disease character-ized by osteoarticular and cutaneous manifestations, the latterincluding nodular and fulminans acne, hidradenitis suppurativaand palmoplantar pustulosis.3 Thus, AF is considered part of theSAPHO spectrum.1Oral isotretinoin (13-cis retinoic acid) is recommended forthe treatment of severe nodular acne.4 It has also been used inAF1 that, paradoxically, can be triggered by isotretinoin.5We report two male adolescents with isotretinoin-triggeredAF and severe osteoarticular manifestations. In both cases, treat-ment with a recombinant IL-1 receptor antagonist, anakinra,bisphosphonates and a short course of corticosteroids led torapid disease control.A 17-year-old male was treated with 0.6 mg/kg/day oral iso-tretinoin for nodular acne. After 4 weeks, he presented ulceratednodules on the face and trunk healing with hypertrophic scars(Fig. 1), associated with back, chest and hip pain, joint swellingand functional impairment. Isotretinoin was discontinued.C-reactive protein was 3.23 mg/dL, ESR 46 mm/h and WBCcount 14 000/lL (neutrophils 83.9%). Whole-body magneticresonance imaging (MRI) revealed sternoclavicular jointinvolvement extending to the clavicles, soft tissues and sternum,as well as multiple hyperintense lesions of L2 vertebra, left iliaccrest and left distal femoral metaphysis (Fig. 1). Bone scintigra-phy showed increased uptake at the same structures (Fig. 1). Weadministered prednisone (0.8 mg/kg/day) tapered over 2 weeks,three pamidronate intravenous infusions (1 mg/kg) and ana-kinra subcutaneous injections (100 mg/day) for 3 months. Amarked osteoarticular and cutaneous improvement wasobserved within 2 weeks, with clinical remission in 1 monthwithout side-effects. Follow-up MRI documented lesion resolu-tion and the disease did not recur over the last 3 years.The second patient, a 17-year-old male, was admitted to ouremergency department for back and chest pain, weight loss andlow-grade fever in the last 10 days. Isotretinoin (0.8 mg/kg/day)had been administered for severe acne for 6 weeks and stopped5 days before. Physical examination revealed cystic and ulceratedacne, reduced hip movement range with sternal and lumbarspine pain. C-reactive protein was 2.68 mg/dL, ESR 35 mm/hand WBC count 12 010/lL (71.7% neutrophils). Whole-bodyMRI and bone scintigraphy showed sternoclavicular, rightshoulder, sacroiliac and long bone involvement. We adminis-tered prednisone 2 mg/kg/day, gradually tapered over 8 weeks,three pamidronate infusions (1 mg/kg) and anakinra (100 mg/day), with marked reduction of symptoms within 2 weeks. Fol-low-up MRI and bone scintigraphy performed at 7, 12 and(a) (b)(c) (d)(e) (f)Figure 1 Case 1: Confluent papulonodular and cystic inflamma-tory acne lesions on the right cheek shortly after isotretinoin dis-continuation (a); residual erythema and scarring in the same areasafter 2-week anakinra treatment (b). Contiguous sagittal and coro-nal whole-body STIR MR image (c–e) and whole-body bone scan99mTc-MDP (f). Sternoclavicular involvement extending to theclavicles, the soft tissues and the sternum (c, arrows). Hyperinten-sity of the left iliac crest (d, arrow) and adjacent soft tissue, and leftdistal femoral metaphysis (d, arrow). L2 vertebra hyperintensity (e,arrow). Increased radiotracer uptake at the same areas (f, arrows).© 2016 European Academy of Dermatology and VenereologyJEADV 2016JEADV18 months revealed a progressive improvement. Anakinra ther-apy is still ongoing 2 years after discharge (100 mg every3 days), without side-effects.Understanding of SAPHO pathogenesis is still limited. Proin-flammatory cytokines such as TNF-a and IL-1 seem to play acentral role,6–8 and the recombinant IL-1 receptor antagonistanakinra has proven rapidly effective in a limited number ofpatients with SAPHO syndrome7–10 (Table 1).Although mild and transient myalgia and arthralgia are fre-quent during isotretinoin treatment, severe osteoarticular mani-festations of AF occur rarely, usually within few weeks fromisotretinoin starting.5 This suggests a possible genetic suscepti-bility to SAPHO.In conclusion, we describe for the first time the successful useof anakinra in two cases of AF presenting radiologically docu-mented osteoarticular manifestations. The rapid and sustainedosteoarticular and acne therapeutic response is in keeping withthe IL-1 role in SAPHO pathogenesis. Of note, the combinedtherapy with anakinra and pamidronate allowed to significantlyshorten corticosteroid course.Bone scintigraphy alterations observed in about 70% of AFcases2 indicate that the large majority of patients with AF haveSAPHO syndrome. Patients with AF should be systemicallyscreened by whole-body bone scintigraphy and/or MRI to ascer-tain osteoarticular lesions, and ensure an appropriate manage-ment and follow-up.T. Oranges,1 A. Insalaco,2 A. Diociaiuti,3 C. Carnevale,3R. Strippoli,4 G. Zambruno,3 P. Toma,5 M. El Hachem3,*1Department of Dermatology, Pisa University, Pisa, Italy, 2Division ofRheumatology, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy,3Dermatology, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy,4Department of Cellular Biotechnologies and Hematology, Section ofMolecular Genetics, Sapienza University, Rome, Italy, 5Department ofImaging, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy*Correspondence: M. El Hachem. E-mail: may.elhachem@opbg.netReferences1 Zaba R, Schwartz R, Jarmuda S, Czarnecka-Operacz M, Silny W. Acnefulminans: explosive systemic form of acne. J Eur Acad Dermatol Venereol2011; 25: 501–507.2 Laasonen LS, Karvonen SL, Reunala TL. Bone disease in adolescents withacne fulminans and severe cystic acne: radiologic and scintigraphic find-ings. AJR Am J Roentgenol 1994; 162: 1161–1165.3 Nguyen MT, Borchers A, Selmi C, Naguwa SM, Cheema G, GershwinME. The SAPHO syndrome. Semin Arthritis Rheum 2012; 42: 254–265.4 Nast A, Dreno B, Bettoli V et al. European evidence-based (S3) guidelinefor the treatment of acne – update 2016 – short version. J Eur AcadDermatol Venereol 2016; 30: 1261–1268.5 Barbareschi M, Paresce E, Chiaratti A, Ferla Lodigiani A, Clerici G,Greppi F. Unilateral sacroiliitis associated with systemic isotretinointreatment. Int J Dermatol 2010; 49: 331–333.6 Cassel SL, Janczy JR, Bing X et al. Inflammasome-independent IL-1bmediates autoinflammatory disease in Pstpip2-deficient mice. Proc NatlAcad Sci USA 2014; 111: 1072–1077.7 Firinu D, Garcia-Larsen V, Manconi PE, Del Giacco SR. SAPHO syn-drome: current developments and approaches to clinical treatment. CurrRheumatol Rep 2016; 18: 35.8 Firinu D, Murgia G, Lorrai MM et al. Biological treatments for SAPHOsyndrome: an update. Inflamm Allergy Drug Targets 2014; 13: 199–205.9 Colina M, Pizzirani C, Khodeir M et al. Dysregulation of P2X7 receptor-inflammasome axis in SAPHO syndrome: successful treatment with ana-kinra. Rheumatology (Oxford) 2010; 49: 1416–1418.10 Wendling D, Prati C, Aubin F. Anakinra treatment of SAPHO syndrome:short-term results of an open study. Ann Rheum Dis 2012; 71: 1098–1100.DOI: 10.1111/jdv.14022Table 1 Cases of SAPHO syndrome treated with anakinraPatientnumberAge Sex SAPHO skinmanifestationPrevious therapies Response totreatment (weeks)Loss of efficacyand relapsesAdversereactionReference1 54 F PPP NSAIDs, CCS, MTX,LEFYes (1) No Yes* 92 41 M PPP NSAIDs, CCS,colchicines, SSZ, retinoidsYes (<2) No No 93 49 F HS NSAIDs, MTX, INFX,retinoidsYes (2) No No 94 53 F PPP NSAIDs, CCS, MTX,colchicines, INFX,ETN, ADAYes (4) No No 95 25 F PPP NSAIDs, pamidronate Yes (2) No No 96 37 M PPP NSAIDs, pamidronate,ETN, ADANo No No 97 47 F PPP SSZ Yes (8) No No 88 NS NS PPP NSAIDs, CCS, LEF, MTX,pamidronate, tetracyclines,INFX, ETN, ADAYes (rapid action) No Yes* 7CCS, corticosteroids; MTX, methotrexate; LEF, leflunomide; SSZ, sulfasalazine; INFX, infliximab; ETN, etanercept; ADA, adalimumab; PPP, palmoplantarpustulosis; HS, hidradenitis suppurativa; NS, not specified.*Injection site reaction.© 2016 European Academy of Dermatology and VenereologyJEADV 20162 Letter to the Editor

Severe osteoarticular involvement in isotretinoin-triggered acne fulminans: two cases successfully treated with anakinra.

T. Oranges

A. Insalaco

A. Diociaiuti

C. Carnevale

R. Strippoli

P. Tomà

M. El Hachem

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Journal of the European Academy of Dermatology and Venereology

Severe osteoarticular involvement in isotretinoin-triggered acne fulminans: two cases successfully treated with anakinra

https://iris.uniroma1.it/bitstream/11573/1184953/1/Oranges_Severe-osteoarticular_2017.pdf

Severe osteoarticular involvement in isotretinoin-triggered acne fulminans: two cases successfully treated with anakinra.

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