Die Sarkoidose aus dermatologischer Perspektive

Zusammenfassung

Die Sarkoidose ist eine seltene Multisystemerkrankung, welche durch nicht-verkäsende Granulome charakterisiert ist, die sich an verschiedenen Organen manifestieren können. Die Pathogenese der Sarkoidose ist nicht vollständig geklärt, neben genetischen Faktoren spielen auch infektiöse Triggerfaktoren sowie Umwelteinflüsse eine Rolle. Die Lunge ist bei über 90 % der Patienten betroffen und damit das am häufigsten involvierte Organ. Es folgt die Haut, die bei bis zu einem Drittel der Sarkoidose-Patienten Auffälligkeiten aufweist, welche anderen Organbeteiligungen häufig vorausgehen. Es ist daher wichtig, die Sarkoidose der Haut frühzeitig zu diagnostizieren, damit eine symptomorientierte Durchuntersuchung und Therapie in die Wege geleitet werden können. Letztere gestaltet sich oft schwierig, da evidenzbasierte Therapieempfehlungen weitgehend fehlen.

In dieser Übersichtarbeit werden die dermatologische Vielgestaltigkeit der Erkrankung, die empfohlenen fachspezifischen und fachübergreifenden Untersuchungen sowie die Therapiemöglichkeiten vorgestellt und diskutiert.

Abstract

Sarcoidosis is a rare multisystemic disease characterized by non-caseating granuloma, which can manifest in a variety of organs. The pathogenesis of sarcoidosis is largely unknown; genetic factors, microbial triggers and environmental agents appear to play a role.

While pulmonary sarcoidosis is the most abundant organ manifestation (> 90 % of patients), involvement of the skin is the most common extrapulmonary presentation of the disease that occurs in up to one third of the patients. Skin manifestations often preceed further organ involvement. It is therefore crucial to early diagnose this rare skin disease in order to initiate essential organ diagnostics to exclude or confirm extracutaneous manifestations and to eventually start therapy. Treatment of sarcoidosis remains difficult; evidence-based therapy guidelines and clinical studies are widely lacking.

Herein we describe the manifold dermatological presentations of sarcoidosis and suggest dermatologic and interdisciplinary diagnostic investigations. Based on the diagnosed manifestations we present and discuss therapeutical options.

• Literatur

• 1 Mana J, Rubio-Rivas M, Villalba N. et al. Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: Cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona, Spain. Medicine (Baltimore) 2017; 96: e7595
• 2 Valeyre D, Prasse A, Nunes H. et al. Sarcoidosis. Lancet 2014; 383: 1155-1167
• 3 Schurmann M, Reichel P, Muller-Myhsok B. et al. Results from a genome-wide search for predisposing genes in sarcoidosis. Am J Respir Crit Care Med 2001; 164: 840-846
• 4 Iannuzzi MC, Iyengar SK, Gray-McGuire C. et al. Genome-wide search for sarcoidosis susceptibility genes in African Americans. Genes Immun 2005; 6: 509-518
• 5 Liu KL, Tsai WC, Lee CH. Cutaneous sarcoidosis: A retrospective case series and a hospital-based case-control study in Taiwan. Medicine (Baltimore) 2017; 96: e8158
• 6 Cozier YC. Assessing the worldwide epidemiology of sarcoidosis: challenges and future directions. Eur Resp J 2016; 48: 1545-1548
• 7 Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007; 357: 2153-2165
• 8 Esteves T, Aparicio G, Garcia-Patos V. Is there any association between Sarcoidosis and infectious agents? a systematic review and meta-analysis. BMC Pulm Med 2016; 16: 165
• 9 Jamilloux Y, Cohen-Aubart F, Chapelon-Abric C. et al. Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: A multicenter study of 132 patients. Sem Arthritis Rheum 2017; 288-294
• 10 Amber KT, Bloom R, Mrowietz U. et al. TNF-alpha: a treatment target or cause of sarcoidosis?. J Eur Acad Dermatol Venereol 2015; 29: 2104-2111
• 11 Collins LK, Chapman MS, Carter JB. et al. Cutaneous adverse effects of the immune checkpoint inhibitors. Curr Probl Cancer 2017; 41: 125-128
• 12 Al-Kofahi K, Korsten P, Ascoli C. et al. Management of extrapulmonary sarcoidosis: challenges and solutions. Ther Clin Risk Manag 2016; 12: 1623-1634
• 13 Garweg JG. [Sarcoidosis and uveitis: An update]. [Article in German] Ophthalmologe 2017; 114: 525-533
• 14 Weidenthaler-Barth B, Steinbrink K, Kummel A. et al. [Sarcoidosis: Organ involvement, diagnosis, current treatment]. [Article in German] Hautarzt 2015; 66: 549-563
• 15 Haimovic A, Sanchez M, Judson MA. et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. Extracutaneous disease. J Am Acad Dermatol 2012; 66: 719 e1 – 10; quiz 729 – 730
• 16 Giner T, Benoit S, Kneitz H. et al. [Sarcoidosis: Dermatological view of a rare multisystem disease]. [Article in German] Hautarzt 2017; 68: 526-535
• 17 Chowaniec M, Starba A, Wiland P. Erythema nodosum – review of the literature. Reumatologia 2016; 54: 79-82
• 18 Haimovic A, Sanchez M, Judson MA. et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. Cutaneous disease. J Am Acad Dermatol 2012; 66: 699 e1 – 18; quiz 717 – 698
• 19 Esteves TC, Aparicio G, Ferrer B. et al. Prognostic value of skin lesions in sarcoidosis: clinical and histopathological clues. Eur J Dermatol 2015; 25: 556-562
• 20 Ungprasert P, Wetter DA, Crowson CS. et al. Epidemiology of cutaneous sarcoidosis, 1976 – 2013: a population-based study from Olmsted County, Minnesota. J Eur Acad Dermatol Venereol 2016; 30: 1799-1804
• 21 Uysal P, Durmus S, Sozer V. et al. YKL-40, Soluble IL-2 Receptor, Angiotensin Converting Enzyme and C-Reactive Protein: Comparison of Markers of Sarcoidosis Activity. Biomolecules 2018; 8: pii: E84
• 22 Thi Hong Nguyen C, Kambe N, Kishimoto I. et al. Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement. J Dermatol 2017; 44: 789-797
• 23 Ziegenhagen MW, Rothe ME, Schlaak M. et al. Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis. Eur Respir J 2003; 21: 407-413
• 24 Lima AL, Goetze S, Illing T. et al. Light and Laser Modalities in the Treatment of Cutaneous Sarcoidosis: A Systematic Review. Acta Derm Venereol 2018; 98: 481-483
• 25 Baughman RP, Lower EE. Medical therapy of sarcoidosis. Semin Respir Critical Care Med 2014; 35: 391-406
• 26 Jones E, Callen JP. Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas. J Am Acad Dermatol 1990; 23: 487-489
• 27 Doherty CB, Rosen T. Evidence-based therapy for cutaneous sarcoidosis. Drugs 2008; 68: 1361-1383
• 28 Mosam A, Morar N. Recalcitrant cutaneous sarcoidosis: an evidence-based sequential approach. J Dermatolog Treat 2004; 15: 353-359
• 29 Marmor MF, Kellner U, Lai TY. et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016; 123: 1386-1394
• 30 Kouba DJ, Mimouni D, Rencic A. et al. Mycophenolate mofetil may serve as a steroid-sparing agent for sarcoidosis. Br J Dermatol 2003; 148: 147-148
• 31 Bachelez H, Senet P, Cadranel J. et al. The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol 2001; 137: 69-73
• 32 Pariser RJ, Paul J, Hirano S. et al. A double-blind, randomized, placebo-controlled trial of adalimumab in the treatment of cutaneous sarcoidosis. J Am Acad Dermatol 2013; 68: 765-773
• 33 Drake WP, Oswald-Richter K, Richmond BW. et al. Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study. JAMA Dermatol 2013; 149: 1040-1049