Resolution of cutaneous sarcoidosis after Janus kinase inhibitor therapy for concomitant polycythemia vera

Wei, Jiake; Kallenbach, Lisa R.; Kreider, Maryl; Leung, Thomas; Rosenbach, Misha

doi:10.1016/j.jdcr.2019.02.006

Cited by 49 publications

(35 citation statements)

References 8 publications

(8 reference statements)

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“…Inhibition of this pathway with a JAK inhibitor disrupts these cytokine signals between T cells and macrophages (Figure F). Improvement in concomitant sarcoidosis has also been reported in two patients with myelodysplastic disorders treated with ruxolitinib, a JAK1 and JAK2 inhibitor, and in a third patient with sarcoidosis‐like systemic granulomatosis also treated with ruxolitinib .…”

Section: Discussionmentioning

confidence: 72%

Treatment of Multiorgan Sarcoidosis With Tofacitinib

Damsky

Young

Sloan

et al. 2020

ACR Open Rheumatology

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Objective. Sarcoidosis is an idiopathic inflammatory disorder that is difficult to treat. There is accumulating evidence that constitutive activation of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling occurs in sarcoidosis and represents a target for treatment. Here we report the efficacy of tofacitinib, a Janus kinase (JAK) inhibitor, in a single patient with multiorgan sarcoidosis.Methods. A patient with long-standing multiorgan sarcoidosis who was unresponsive to other commonly used therapies, including methotrexate, prednisone, and tumor necrosis factor α blockade, was treated with tofacitinib.Results. Tofacitinib treatment resulted in clinical remission of cutaneous sarcoidosis lesions and resolution of positron emission tomography avid lesions in internal organs after 6 months. An evaluation of lesional tissue and blood before and during treatment showed resolution of granulomatous inflammation and normalization of disease biomarkers.Conclusion. This case illustrates the promise of JAK inhibition as a strategy to treat recalcitrant sarcoidosis and suggests that further study of JAK inhibitors in sarcoidosis is needed.

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Section: Discussionmentioning

confidence: 72%

Treatment of Multiorgan Sarcoidosis With Tofacitinib

Damsky

Young

Sloan

et al. 2020

ACR Open Rheumatology

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“…IL-17 inhibitors have been reported to induce granulomatous inflammation in early reports. 98 JAK inhibitors have been reported in isolated case reports as beneficial for sarcoidosis, [99][100][101] as well as other granulomatous diseases, 97,[102][103][104] and offer promise as a potential emerging treatment for sarcoidosis (►Table 2).…”

Section: Tnf Inhibitorsmentioning

confidence: 99%

Cutaneous Sarcoidosis

Caplan

Rosenbach

Imadojemu

2020

Semin Respir Crit Care Med

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Sarcoidosis is a chronic, multisystem, inflammatory disorder of unknown etiology that is characterized by noncaseating granulomas that impair normal organ functioning. Sarcoidosis predominantly affects the lungs, but the skin is often cited as the second most frequently involved organ. Cutaneous manifestations of sarcoidosis are highly variable and ongoing research seeks to better understand the relationship between clinical morphology and disease prognosis. Skin findings in patients with sarcoidosis can be “specific,” in which sarcoidal granulomas infiltrate the skin, or they can represent a “nonspecific” reactive inflammatory process, as is seen in calcinosis cutis and erythema nodosum. Cutaneous sarcoidosis can be the initial presenting sign or develop later in the course of the disease. In some patients, the skin will be the most involved and impactful organ system and will drive therapy. In other cases, the skin will be an incidental or minor finding, but may be easily accessible for biopsy to confirm the diagnosis. There are many potential therapies for sarcoidosis, though no one therapy is universally effective.

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“…149 Four case reports of sarcoidosis patients treated with JAK inhibitors (tofacitinib or ruxolitinib) are currently available, but none of these patients had ocular involvement. [150][151][152][153] Paley et al described two patients with refractory anterior uveitis or scleritis, who could not tolerate immunosuppressants or ADA, and whose ocular disease improved upon tofacitinib treatment. 154 Nevertheless, both were treated with concurrent MTX and the specific effect of tofacitinib remains difficult to establish.…”

Section: Anti-tnf-α Treatmentmentioning

confidence: 99%

Ocular Sarcoidosis

Sève

Jamilloux

Tilikete

et al. 2020

Semin Respir Crit Care Med

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Sarcoidosis is one of the leading causes of inflammatory eye disease. Any part of the eye and its adnexal tissues can be involved. Uveitis and optic neuropathy are the main manifestations, which may require systemic treatment. Two groups of patients with sarcoid uveitis can be distinguished: one of either sex and any ethnicity in which ophthalmological findings are various and another group of elderly Caucasian women with mostly chronic posterior uveitis. Clinically isolated uveitis revealing sarcoidosis remains a strictly ocular condition in a large majority of cases. Although it can be a serious condition involving functional prognosis, early recognition in addition to a growing therapeutic arsenal (including intravitreal implant) has improved the visual prognosis of the disease in recent years. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema. In up to 30% of the cases that require an unacceptable dosage of corticosteroids to maintain remission, additional immunosuppression is used, especially methotrexate. As with other forms of severe noninfectious uveitis, monoclonal antibodies against tumor necrosis factor-α have been used. However, only very rarely does sarcoid uveitis fail to respond to combined corticosteroids and methotrexate therapy, a situation that should suggest either poor adherence or another granulomatous disease. Optic neuropathy often affects women of African and Caribbean origins. Some authors recommend that patients should be treated with high-dose of corticosteroids and concurrent immunosuppression from the onset of this manifestation, which is associated with a poorer outcome.

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Resolution of cutaneous sarcoidosis after Janus kinase inhibitor therapy for concomitant polycythemia vera

Cited by 49 publications

References 8 publications

Treatment of Multiorgan Sarcoidosis With Tofacitinib

Treatment of Multiorgan Sarcoidosis With Tofacitinib

Cutaneous Sarcoidosis

Ocular Sarcoidosis

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