Lupus Pernio

Article Author:
Azza Redissi
Article Editor:
Noureddine Litaiem
Updated:
6/3/2019 5:11:20 PM
PubMed Link:
Lupus Pernio

Introduction

Lupus pernio is a specific cutaneous manifestation of sarcoidosis. It was first described in 1889 by Ernest Besnier as a chronic violaceous lesion typically located on the nose, cheeks, ears, and fingers.[1] It is one feature of a multisystem disease and is often associated with severe organ involvement including lungs and upper respiratory tract.[2] Its impact is mainly aesthetic as it can result in disfiguring skin lesions that are challenging to treat. Recognizing specific cutaneous lesions of sarcoidosis is important as they are easily accessible to biopsy and offer an important clue to diagnosis.

Etiology

The etiology of sarcoidosis remains poorly understood. It is a granulomatous multisystem disease characterized by hyperactivity of the cell-mediated immune system, typically CD4+ T lymphocytes. The hypothesis of its multifactorial origin is widely accepted, resulting from a complex interaction between genetic susceptibility and environmental triggers.[3]

Epidemiology

Although the epidemiology of sarcoidosis has been widely investigated, the real incidence of the disease remains difficult to determine, mainly due to highly variable clinical presentation and the large proportion of asymptomatic cases. Studies report a greater prevalence of the disease in northern Europe, the highest being in Sweden (64 persons per 100,000 population).[4] A higher incidence of the disease is observed in women and black people.[4] Sarcoidosis most commonly affects the 25- to 40-year age groups; however, a second peak in women older than 50 years has also been described.[4] Cutaneous involvement in sarcoidosis is observed in 25% to 33% of patients.[5] Lupus pernio is characterized by a later age of onset, is twice as prevalent in females and is most common in African American women.[6][7]

Histopathology

The presence of epithelioid cell granulomas with a variety of langerhan giant cells devoid of caseous necrosis is the histopathologic hallmark of the disease. Occasional areas of fibrinoid necrosis at the center of the granuloma may be identified. Other cytoplasmic structures can be observed within the granulomas, including Schaumann bodies and asteroid bodies, although they are neither specific nor required for the diagnosis.

History and Physical

Lupus pernio is characterized by chronic, persistent, indolent, indurated, red-purple or violaceous nodular cutaneous lesions that usually affect the nose, cheeks, ears, lips, eyelids, forehead, and fingers. It ranges from a few small nodules on the nose to exuberant plaques spreading across both cheeks.[8] Lesions of lupus pernio start insidiously, increase gradually in size, can coalesce, and become progressively disfiguring.

Evaluation

Lupus pernio is only one feature of a multisystem disorder. It has a high predictive value for both pulmonary parenchymal involvement and upper respiratory tract. In a study of 35 patients with lupus pernio,[7] association with intrathoracic involvement was observed in 74% of cases, upper respiratory tract disease in 54% of patients, peripheral lymphadenopathy in 43% of cases, ocular involvement in 37% of cases, and accompanying cutaneous lesions including plaques, nodules, cheloids, and erythema nodosum in 26% of patients.

Therefore, a workup for extensive systemic sarcoidosis should be undertaken right after diagnostic confirmation. In addition to a complete history and thorough physical examination, initial evaluation should also include chest x-ray, pulmonary function tests, electrocardiogram, and ophthalmologic examination (slit-lamp and fundus examination). A tuberculin skin test should also be performed and is negative in 83% of cases indicating a lower ability to acquire and express delayed hypersensitivity.[7] Laboratory analysis should particularly assess blood and urine calcium levels as well as renal and hepatic functions. C-reactive protein level and erythrocyte sedimentation rate are often elevated nonspecific findings. A high serum angiotensin-converting enzyme level, although not specific of sarcoidosis and increased in only 60% of patients with sarcoidosis,[9] can add support to the diagnosis, and is particularly useful as a monitor for the disease’s progression and activity.

Further explorations will be indicated according to the suspected involved organ, e.g., computed tomography scanning of the chest or endoscopic examination to confirm lung and upper respiratory tract involvement, or hand and feet radiographs showing bone cysts when digits are involved.[7]

If no systemic involvement is initially found, a long-term follow-up with close clinical and radiological supervision must be undertaken, as most patients will develop systemic symptoms later on the course of the disease.

Treatment / Management

No treatment was proved to be uniformly effective. For limited cutaneous involvement, high potency topical and intralesional steroids can be used, but results are limited, and recurrence is high.[10] Treatment often must be more aggressive to achieve good results and avoid scarring. Local and systemic steroids, as well as antimalarials, are the mainstay of treatment for lupus pernio, but a flare-up is often observed following tapering of the corticosteroids. Methotrexate is a valuable adjunct in the treatment to avoid relapses and prevent side effects from prolonged steroid use.[11] Thalidomide has also been proven to be effective.[12] More recent therapeutics, specifically tumor necrosis factor (TNF)-alpha inhibitors, are a good alternative treatment for severe lesions that have not responded to more conventional therapies.[13] Successful treatment with adalimumab has been reported,[14] and in a study comparing 116 treatment courses in 54 patients,[15] infliximab appeared to be superior to other therapeutic agents in treating refractory lupus pernio.

Deforming lesions, however, respond poorly to medical management, and in these cases, surgery can be performed,[16] but often yields suboptimal cosmetic results. Carbon dioxide laser is a good alternative for irreversible disfiguring lesions and offers better aesthetic results despite possible hypopigmentation of the treated areas.[17][18]

Differential Diagnosis

The distinctive appearance of lupus pernio makes it an easily recognizable manifestation of sarcoidosis. However, a few differential diagnoses can mimic its clinical presentation, including fungal infection, lupus vulgaris, leishmaniasis, berylliosis, lymphoma cutis, lupus erythematosus and tuberculoid leprosy that has a similar pattern of distribution. The cutaneous examination is usually enough to differentiate most of these lesions, but in some cases, a biopsy is necessary for definitive diagnosis.

Prognosis

Lupus pernio is not life-threatening, but its psychological impact may affect the patient’s quality of life. Besides being a chronic and potentially disfiguring lesion, lupus pernio is a predictive factor of more progressive sarcoidosis with a prolonged course and a more severe thoracic and extra-thoracic involvement.[2] Therefore, this form of sarcoidosis often portends a poor prognosis.

Complications

When located on the face, head and neck lesions of lupus pernio can be quite mutilating. They can impair mouth and eyelid movement, and when encountered on the ala, they can obstruct the nasal airway.[18] Granulomatous infiltration of the nasal mucosa and bone can also complicate lupus pernio, occasionally resulting in ulceration and septal perforation.[8] Furthermore, the emotional scarring that this physical disfigurement causes should not be underestimated. However, the most severe complications are related to vital organs involvement, including lungs, heart, and nervous system.

Deterrence and Patient Education

Patients with sarcoidosis should be informed about their diagnosis, its chronical course, the different organs the disease can affect and the possible systemic symptoms they may present. They should also be educated about the importance of regular follow-up, the treatments they are taking, their possible side effects and the dangers of premature interruption of medication.

Enhancing Healthcare Team Outcomes

Patients with lupus pernio are usually initially seen by a dermatologist. The coordination between the dermatologist and the pathologist is essential, as non-caseating granulomas are not pathognomonic of sarcoidosis, but the distinctive clinical presentation can guide the diagnosis. After confirmation of the disease, patients are generally referred to internal medicine specialists for follow-up. Giving that sarcoidosis is a systemic disease, an interprofessional team of healthcare professionals is required for the management of patients, including radiologists, pulmonologists, ophthalmologists, otolaryngologists, cardiologists, and neurologists.[19] (Level V) Psychologists can also play an important role in managing the psychological impact of the disease.



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References

[1] Stam J, [Sarcoidosis or Besnier-Boeck-Schaumann disease]. Tijdschrift voor ziekenverpleging. 1980 Aug 26     [PubMed PMID: 6903029]
[2] Mañá J,Marcoval J,Graells J,Salazar A,Peyrí J,Pujol R, Cutaneous involvement in sarcoidosis. Relationship to systemic disease. Archives of dermatology. 1997 Jul     [PubMed PMID: 9236527]
[3] Chen ES,Moller DR, Etiology of sarcoidosis. Clinics in chest medicine. 2008 Sep     [PubMed PMID: 18539232]
[4] Mateyo K,Thomeer M, Sarcoidosis around the Globe. Seminars in respiratory and critical care medicine. 2017 Aug     [PubMed PMID: 28750456]
[5] Yanarda─č H,Pamuk ON,Karayel T, Cutaneous involvement in sarcoidosis: analysis of the features in 170 patients. Respiratory medicine. 2003 Aug     [PubMed PMID: 12924527]
[6] Marchell RM,Judson MA, Cutaneous sarcoidosis. Seminars in respiratory and critical care medicine. 2010 Aug     [PubMed PMID: 20665394]
[7] Spiteri MA,Matthey F,Gordon T,Carstairs LS,James DG, Lupus pernio: a clinico-radiological study of thirty-five cases. The British journal of dermatology. 1985 Mar     [PubMed PMID: 2983750]
[8] James DG, Lupus pernio. Lupus. 1992 May     [PubMed PMID: 1301972]
[9] Rømer FK, Clinical and biochemical aspects of sarcoidosis. With special reference to angiotensin-converting enzyme (ACE). Acta medica Scandinavica. Supplementum. 1984     [PubMed PMID: 6097101]
[10] Khatri KA,Chotzen VA,Burrall BA, Lupus pernio: successful treatment with a potent topical corticosteroid. Archives of dermatology. 1995 May     [PubMed PMID: 7741556]
[11] Webster GF,Razsi LK,Sanchez M,Shupack JL, Weekly low-dose methotrexate therapy for cutaneous sarcoidosis. Journal of the American Academy of Dermatology. 1991 Mar     [PubMed PMID: 2061444]
[12] Nguyen YT,Dupuy A,Cordoliani F,Vignon-Pennamen MD,Lebbé C,Morel P,Rybojad M, Treatment of cutaneous sarcoidosis with thalidomide. Journal of the American Academy of Dermatology. 2004 Feb     [PubMed PMID: 14726878]
[13] Blanco R,González-Gay MA,González-López MA,Fernández-Llaca H,González-Vela MC, Refractory highly disfiguring lupus pernio: a dramatic and prolonged response to infliximab. International journal of dermatology. 2015 Aug     [PubMed PMID: 26147319]
[14] Judson MA, Successful treatment of lupus pernio with adalimumab. Archives of dermatology. 2011 Nov     [PubMed PMID: 22106129]
[15] Stagaki E,Mountford WK,Lackland DT,Judson MA, The treatment of lupus pernio: results of 116 treatment courses in 54 patients. Chest. 2009 Feb     [PubMed PMID: 18812454]
[16] Smith R,Haeney J,Gulraiz Rauf Kh, Improving cosmesis of lupus pernio by excision and forehead flap reconstruction. Clinical and experimental dermatology. 2009 Jul     [PubMed PMID: 19508469]
[17] O'Donoghue NB,Barlow RJ, Laser remodelling of nodular nasal lupus pernio. Clinical and experimental dermatology. 2006 Jan     [PubMed PMID: 16309473]
[18] Stack BC Jr,Hall PJ,Goodman AL,Perez IR, CO2 laser excision of lupus pernio of the face. American journal of otolaryngology. 1996 Jul-Aug     [PubMed PMID: 8827292]
[19] Dubaniewicz A, [The diagnostic algorithm of practice in pulmonary and extrapulmonary sarcoidosis]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2018 Mar 27     [PubMed PMID: 29601557]