Title: Neurosarcoidosispresenting with lupus pernio and painless vision loss. “Right in front ofyour face…” Authors (mailingaddress and emails): Margaret L. Pfeiffer, MD,1,2 Eric.
L. Crowell,MD,1,2 Ore-ofe O. Adesina, MD1,2 1 Ruiz Department of Ophthalmology and VisualScience, McGovern Medical School at The University of Texas Health ScienceCenter at Houston; 2 Robert Cizik Eye Clinic; 3 Department of Neurology, McGovern MedicalSchool at The University of Texas Health Science Center at Houston Abstract: (willfinish when the paper content in finalized) Keywords: Neurosarcoidosis,lupus pernio, painless vision loss, noncaseating granuloma, orbital apex mass Introduction: Wepresent a case of neurosarcoidosis presenting concurrently with cutaneous lupuspernio (Some case reports don’t include an introduction but rather just anabstract) Case Report: A54-year-old African American woman with a history of diabetes and hypertensionpresented with a 2-week history of painless left-sided vision loss and a6-month history of a slow growing cutaneous lesion between the right medialcanthus and nasal bridge (figure 1). Best-corrected visual acuity was 20/25 onthe right and counting fingers on the left with a left relative afferentpupillary defect. Humphrey visual field automated perimetry (Stim V OD, StimIII OS; Carl Zeiss Meditec, Dublin, CA) showed peripheral constriction in theright eye and temporal and superonasal defects in the left eye (figure 2). Anteriorsegment and dilated fundus examinations were unremarkable. MRI with contrastshowed irregular, nodular enhancement of both optic nerve sheaths with a 4 x 4 x2 mm nodular enhancing mass abutting the medial aspect of the left optic nervejust posterior to the orbital apex (figure 3).
There were an additional 3extra-axial enhancing lesions along the superior margin of the left tentorium,the medial aspect of the right middle cranial fossa, and the vertex (figure 4).Workup revealed normal CBC, ANA, ACE level, and lysozyme. CSF analysis showed amild lymphocytic pleocytosis with normal glucose and negative cytology (table1). Punch biopsy of the cutaneous lesion on the nasal bridge revealed noncaseatinggranulomas consistent with sarcoidosis (figure 5). CT of the chest showed hilaradenopathy.
A diagnosis of neurosarcoidosis was made. Treatment with 60 mg oforal prednisone led to rapid improvement of visual acuity to 20/30 in the lefteye, reduction in the size of all of the intracranial masses, includingcomplete resolution of the orbital apex mass compressing the left optic nerve(figure 6-8). She was slowly tapered off of steroids over several weeks and hasremained stable on azathioprine as monotherapy. Laboratory Evaluation (Table 1)CBC: WNL (WBC 8.1, H/H: 13.4/41.9, Plt: 268)ACE: 25 U/LLysozyme: 8.
5 ug/mLANA: negativeLumbar puncture:WBC: 8 (H) Diff: 4 N, 89 L, 7 M)Glucose: 51Cytology: negative Discussion: Sarcoidosisis an idiopathic, multisystem, inflammatory disorder characterized bygranulomatous inflammation predominantly involving the lungs, skin, eye, andorbit. Globally the highest incidence of sarcoidosis is in northern Europeancountries (PIETINALHO, SWIGRIS). However, in the United States AfricanAmericans are three times greater than Caucasians to have the disease (35.3 vs10.9 cases per 100,000) and women are more commonly affected than men (RYBICKI).
The noncaseating granulomas of sarcoidosis are composed of histiocytes, oftencoalescing to form multinucleated giant cells, and are surrounded bylymphocytes (primarily CD4+ T cells), plasma cells and mast cells (SEGAL). Ocularinvolvement has been reported in 25-50% of cases (HUNTER) and nervous systeminvolvement in 5-12% (ROTHOVA, NEWMAN, HEBEL). Neurosarcoidosis can affect anypart of the central nervous system and may present before, after, or with anyother systemic form of sarcoidosis. As with our patient, optic neuropathy mayoccur in sarcoidosis from compressive lesions, however, signs and symptoms canbe similar to those found in multiple sclerosis-associated optic neuritis,orbital inflammatory pseudotumor or optic perineuritis.
Patients often presentwith rapid decrease in vision in one eye (HUNTER). The presence of isolatedneurosarcoidosis is rare and accounts for only 1% of neurosarcoidosis cases.When neurosarcoidosis is diagnosed, 88-94% have pulmonary involvement, 37-55% haveocular involvement, and 30% have cutaneous involvement.
(HEBEL). While symptomaticneurosarcoidosis is present in 5-10% of cases of sarcoidosis, it can be foundin up to 25% of cases of sarcoidosis via postmortem biopsy (HEBEL). Cutaneous lesions associated with sarcoidosis are dividedinto specific and nonspecific manifestations of the disease. Lesions specificto the disease reveal noncaseating granulomas upon histology.
Whilenoncaseating granulomas are specific to the disease, sarcoidosis is a diagnosisof exclusion and other causes of noncaseating granulomas, such as foreign bodyreactions and fungal infections must be ruled out (Mehta). Nonspecific lesions maypresent as a panniculitis, most commonly erythema nodosum. These lesions raisethe suspicion of sarcoidosis, and in the case of noncaseating granulomas orerythema nodosum, are contributory to its diagnosis (MANA, GIUFFRIDA). Lupuspernio is sarcoid-specific cutaneous manifestation of sarcoidosis. It ischaracterized by violaceous, indurated, infiltrative plaques on the centralface, alar rim, nasal tip, or cheeks.
Lupus pernio and plaques are associated with more severe systemicinvolvement and more chronic course, while erythema nodosum is the hallmark ofacute and benign disease, and is associated with a higher rate of spontaneouslyresolving disease (MANA). In the case of our patient, lupus pernio was thefirst presenting sign and allowed for rapid diagnosis and treatment followed byresolution of her symptoms. As with our patient, lupus pernio, along with othercutaneous manifestations of sarcoidosis (excluding erythema nodosum)disproportionately affects African American women (RYBICKI, BAUGHMAN). Womenare more likely than men to have ocular and neurologic involvement and tobe over the age of 40. (BAUGHMAN, IANNUZZI). Due to the low prevalence and heterogeneity ofneurosarcoidosis, treatment strategies are based on observational case studiesand expert opinion. Corticosteroids are first line treatment (SEGAL, O’CONNEL,STEPANOVIC) and suppress inflammatory genes, including interferon-gamma (IFN-?)and tumor necrosis factor (TNF)-alpha, which play important roles in sarcoidgranuloma formation (BEEGLE).
Long-term use of oral corticosteroids has manycautions and relative contraindications, and in the case of our patient couldpotentially exacerbate her diabetes mellitus and hypertension (STERN,WHITWORTH). Global immune suppressantscan be used as adjunctive therapy to oral steroids to enhance outcomes andreduce the duration of the steroid taper while minimizing relapse rates.Azathioprine, methotrexate, hydroxychloroquine, and cyclosporine A have allbeen used for this purpose (SEGAL, VARGAS). With proper immunosuppressive treatment,vision loss related to optic nerve involvement is often reversible. Conclusion: Neurosarcoidosiscan cause vision loss via direct optic nerve sheath involvement and it isimportant to consider this entity in the differential diagnosis of enhancing centralnervous system lesions or vision loss in the setting of erythema nodosum orsarcoidosis specific skin lesions.
Prompt identification of systemicmanifestations and biopsy of a skin nodule characteristic of cutaneoussarcoidosis aided in this patient’s prompt diagnosis and successful treatment.