Sarcoidosis is a chronic multisystem disorder characterized by the formation of noncaseating epithelioid cell granulomas affecting multiple organ systems. The role of the type 1 helper T (TH1) cell in sarcoidal granuloma formation has been well documented, and the TH17 pathway in sarcoidosis is just now being investigated. TH17 cells are also known to involved in the pathogenesis of psoriasis, and the coexistence of sarcoidosis and psoriasis is mechanistically plausible based on potential shared underlying immunologic pathways.
We report a case series of 7 patients with sarcoidosis and psoriasis vulgaris. All patients had psoriasis ranging from limited disease to involvement of 30% of their body surface area and had evidence of pulmonary sarcoidosis. Three of these patients also had cutaneous sarcoidosis, and 1 of these patients had evidence of both psoriasis and sarcoidosis in the same cutaneous specimen.
Conclusions and Relevance
We report a case series of concomitant sarcoidosis and psoriasis, suggesting that common pathogenesis involving the TH1 and TH17 pathways may be responsible for this disease association. Although additional data are needed to clarify this association, this observation may lead to important understanding of the pathophysiologic and therapeutic management in these disorders.
Sarcoidosis is a chronic multisystem disorder of unknown etiology that is characterized by the formation of noncaseating epithelioid cell granulomas affecting multiple organ systems, most commonly including the lungs, skin, and eyes. Active sarcoidal granulomas consist predominantly of aggregates of epithelioid macrophages and CD4+ T cells. Although the overall pathogenesis is poorly understood, the role of the type 1 helper T (TH1) cell in sarcoidal granuloma formation has been well documented, where macrophages activate CD4+ T cells, which then secrete interleukin (IL)-2 and interferon (IFN)-γ.1 The continued release of IFN-γ by CD4+ cells and the proinflammatory cytokines IL-12, IL-18, and tumor necrosis factor (TNF) by activated macrophages promote and stabilize a TH1-predominant phenotype among the CD4+ T cells in sarcoidal granulomas.1
TH17 cells are a relatively newly described subset of T-cells that are involved in the pathogenesis of autoinflammatory disorders, including, and most notably, psoriasis.2 These cells are characterized by their ability to produce a distinct proinflammatory cytokine profile including IL-17A, IL-17F, IL-22, and TNF.2,3 The role of the TH17 pathway in sarcoidosis is just now being elucidated. Prior studies have demonstrated increased IL17+/CD4+ cells and increased levels of IL-17 messenger RNA in bronchoalveolar lavage fluid and peripheral blood, and recent genetic analyses have identified polymorphisms in the IL-23 receptor, supporting the role of IL-23 in the promotion of the TH17 profile in sarcoidosis.4,5
We present a series of 7 patients with concomitant sarcoidosis and psoriasis, which is hypothesized to occur because of a potential overlap in the immunology and inflammatory patterns underlying these diseases. The coexistence of these diseases may suggest overlap between the underlying triggering mechanisms and may provide important insight into therapeutics for these disorders.
A 69-year-old Jamaican man with a history of pulmonary and ocular sarcoidosis presented with a 20-year history of a scaly red rash that began on his scalp and then spread to involve the rest of his body. His medications included inhaled corticosteroids, and he denied other medical problems. The physical examination was notable for indurated violaceous papules involving his periocular, perinasal, and perioral areas and erythematous plaques with silvery scale on his arms, back, buttocks, and legs (Figure 1A and B). Skin biopsies of his left arm and right thigh were performed. Histopathologic findings from his arm demonstrated psoriasiform hyperplasia with underlying compact granulomas in the superficial reticular and papillary dermis that were composed of epithelioid histiocytes, multinucleated giant cells, lymphocytes and neutrophils (Figure 1C). Findings from an evaluation of the skin from his right thigh were consistent with psoriasis (Figure 1D). Results from the laboratory evaluation were notable for an elevated level of angiotensin-converting enzyme (ACE) level at 98 U/L (range, 12-68 U/L) and normal complete blood cell count (CBC), comprehensive metabolic panel (CMP), calcium level, urinalysis (UA), and thyroid stimulating hormone (TSH) level. (To convert ACE to nanokatals per liter, multiply by 16.667.) The chest radiograph was notable for hilar lymphadenopathy. Treatment with methotrexate for both his sarcoidosis and psoriasis was instituted, with improvement after 8 weeks, clearance of the psoriasiform eruption after 3 months, and complete resolution of both processes after 6 months.
There are indurated violaceous papules along his nasal ala consistent with sarcoidosis (A) and psoriatic plaques on his arms (B). A skin biopsy specimen from his arm confirms concomitant involvement of psoriasis and sarcoidosis (C) and a biopsy specimen from his leg demonstrates psoriasis (D). C and D, Hematoxylin-eosin, original magnification ×100.
A 46-year-old woman with a history of albinism and biopsy-proven cutaneous and pulmonary sarcoidosis noted worsening of violaceous nodules on her body. She was legally blind, which was attributed to ocular involvement of sarcoidosis. Despite treatment with oral prednisone, her skin continued to worsen. Other medications included inhaled corticosteroids and ibuprofen. Physical examination demonstrated firm violaceous nodules on her arms, lower legs, and hip (Figure 2A) and scattered, erythematous plaques (Figure 2B). Findings from a skin biopsy specimen from her arm was consistent with psoriasis and distinct from her prior cutaneous sarcoidosis (Figure 2C and D). Laboratory evaluation were remarkable for an ACE level of 107 U/L and normal results for CBC, CMP, calcium and TSH levels, and UA. A chest radiograph and computed tomographic scan demonstrated extensive parenchymal lung disease with bilateral hilar and mediastinal lymphadenopathy. She was started on methotrexate for pulmonary, cutaneous, and ocular sarcoidosis with clearance of her psoriatic lesions within weeks and gradual improvement in her sarcoidosis lesions after approximately 3 months.
Firm violaceous nodule on one arm (A) and psoriatic plaque on her other arm (B). Histopathologic examination confirmed the diagnosis of sarcoidosis (C) and psoriasis, respectively (D). C and D, Hematoxylin-eosin, original magnification ×100.
A 44-year-old man with a 2-year history of psoriasis maintained on narrowband UV-B therapy developed new indurated, mauve-colored plaques on his back, chest, and thighs that were not responsive to therapy and differed from his background psoriatic plaques (Figure 3A). A biopsy of a representative area demonstrated granulomas throughout the dermis (Figure 3B) which differed from his psoriatic disease (Figure 3C). On further review of systems, he had been experiencing dyspnea and previously diagnosed with chronic obstructive pulmonary disorder and heart failure. Additional workup was remarkable for an ACE level of 71 U/L, and normal TSH level and results for CBC, CMP, and UA. Evaluation by a pulmonologist and a cardiac magnetic resonance imaging scan to evaluate for cardiac sarcoidosis are pending. He was started on monotherapy with minocycline, 100 mg twice daily, for his sarcoidosis, and maintained on narrowband UV-B phototherapy (NBUVB) twice weekly for his psoriasis disease; the violaceous erythema and induration of his plaques faded over 2 months, and his psoriasis gradually partially responded to NBUVB.
Indurated, mauve-colored plaques on his leg with classic psoriatic plaque on his knee (A). A skin biopsy specimen demonstrated granulomas throughout the dermis consistent with sarcoidosis (B) distinct from psoriasis (C). B and C, Hematoxylin-eosin, original magnification ×100.
Additional cases seen in our practice over the past 12 months are included in the Table.
We report a case series of 7 patients with both sarcoidosis and psoriasis vulgaris, all of whom had psoriasis that ranged from limited disease to involvement of 30% of their body surface area and evidence of pulmonary sarcoidosis (Table). Three of these patients also had cutaneous sarcoidosis, and 1 of these patients had evidence of both psoriasis and sarcoidosis in the same cutaneous specimen (patient 1) (Figure 1C). Interestingly, multiple patients were treated with methotrexate for both diseases with improvement in both their sarcoidosis and psoriasis. One of the patients received prior treatment with adalimumab for psoriasis and psoriatic arthritis, with this treatment initiated after the diagnosis of pulmonary sarcoidosis had been established. Notably, 2 patients also had a history of deep vein thromboses, although our population is too small to draw any conclusions related to hypercoaguability. The association of sarcoidosis and psoriasis has been rarely reported.6- 9 In these cases, the patients also all had evidence of pulmonary sarcoidosis and cutaneous psoriatic plaques, and in 1 reported case, the patient also had cutaneous sarcoidosis. Because of the rarity of the cases, these reports were felt to be purely coincidental. Sarcoidosis can present with clinically psoriasiform lesions that demonstrate noncaseating granulomas on biopsy; in these cases, the patients were not thought to have psoriasis but rather overlying psoriasiform hyperplasia in the context of sarcoidosis.10,11 In our series, all of the patients had clinical and histologic evidence of cutaneous psoriasis in the presence of sarcoidosis, suggesting an association with these 2 diseases.
The similar pathogenesis of TH1 and TH17 in both sarcoidosis and psoriasis suggest that a common pathway may exist and that the association of these diseases may be more than coincidental. Sarcoidosis, especially sarcoid uveitis, has been demonstrated to be associated with IL23R polymorphism, and suggests that IL23R may be a common susceptibility gene shared by several autoimmune disorders, including psoriasis.12 In 1 study, enhanced IL-17A expression with IL-17A+, IL-17A+IFN-γ+ and IL-17+IL-4+ memory TH cells in sarcoidal granulomas support an important role for TH17 cell involvement in sarcoidosis, as in psoriasis.5 Similarly, upregulation of IL-12, IFN, as well as the TH17 pathway genes IL23 and IL21 but not IL17 were demonstrated in cutaneous sarcoidosis using molecular profiling, suggesting a difference compared with psoriasis and inflammatory bowel disease, in which there is upregulation of IL-17 and the TH17 pathway.4 The exact mechanism and etiologic pathway of sarcoidosis needs to be further elucidated, but overlap with psoriasis is suggested. Similarly, the association of psoriasis with multiple autoimmune diseases was recently evaluated, and psoriasis was associated with 17 of 21 studied autoimmune diseases, suggesting a common genetic or environmental pathway for these diseases.13 Because the TH1 and TH17 pathways are thought to play a role in many inflammatory cutaneous disorders and are not specific for psoriasis or sarcoidosis, this common pathway may explain the observed association, or it is possible that other, unknown interactions common to both of these disease may play an important role. The role of medication-induced diseases also needs to be considered, because certain medications, such as TNF inhibitors, have been reported to induce both psoriatic and sarcoidal lesions.14,15 In this series, this was unlikely given the therapies initiated and the timings of those treatments. One patient received adalimumab, but this was administered after both diagnoses were made.
We report a case series of concomitant sarcoidosis and psoriasis and suggest that these disorders could be related given common pathways of TH1 and TH17, which is important to consider for therapeutic management in these disorders. Our case series is limited by its small sample size, limited geographic sampling, and retrospective analysis. The population of Philadelphia, Pennsylvania, contains a proportionately higher number of African American patients, which could have skewed our results. In addition, in early case series, it is difficult to determine if this observed association is real or occurred by chance. The series does suggest a rare association of 2 overall uncommon diseases. Additional data are needed, particularly large-scale epidemiological, collaborative, or database association studies, to clarify the association.
Accepted for Publication: December 12, 2012.
Corresponding Author: Misha Rosenbach, MD, Department of Dermatology, University of Pennsylvania, 3600 Spruce St, Philadelphia, PA 19104 (firstname.lastname@example.org).
Published Online: June 19, 2013. doi:10.1001/jamadermatol.2013.4256.
Author Contributions: All authors had full access to all of the data in the study and take responsibility for the integrity of the data.
Study concept and design: Schaffer, Rosenbach.
Acquisition of data: Wanat, Schaffer, Richardson, Rosenbach.
Analysis and interpretation of data: Wanat, Schaffer, VanVoorhees, Rosenbach.
Drafting of the manuscript: Wanat.
Critical revision of the manuscript for important intellectual content: Wanat, Schaffer, Richardson, VanVoorhees, Rosenbach.
Obtained funding: Rosenbach.
Administrative, technical, and material support: Wanat, Schaffer, Richardson, Rosenbach.
Study supervision: Rosenbach.
Conflict of Interest Disclosures: Dr VanVoorhees has received grants or honoraria from Amgen, Abbott, Genentech, Warner Chilcott, Janssen, Leo, and Novartis.
Funding/Support: This study was supported in part by a Career Development grant to Dr Rosenbach from the Dermatology Foundation.
Wanat KA, Schaffer A, Richardson V, VanVoorhees A, Rosenbach M. Sarcoidosis and PsoriasisA Case Series and Review of the Literature Exploring Co-Incidence vs Coincidence. JAMA Dermatol. 2013;149(7):848-852. doi:10.1001/jamadermatol.2013.4256