Enlarging plaque on the face with enlarged supraorbital nerve

A 38-year-old Nigerian man, who had been living in Italy since 2008, presented with an annular lesion on the right temporal and frontal region that appeared two months prior to his visit. He reported a slow centrifugal enlargement of the lesion. The man complained about headache and pain radiating to the right frontal region. He was not taking any drugs. Physical examination disclosed an annular plaque of almost 10 x 8 cm in diameter (Figure 1). The margins were raised and slightly edematous, while the skin in the center was not infiltrated but dry and anaesthetic. Edema was observed around the right orbit. The supraorbital nerve was thickened and palpable (Figure 1, white arrow). Skin biopsy showed a multifocal superficial and deep granulomatous dermatitis with epithelioid granulomas (Figures 2 and 3) with perineural distribution. The granulomas were also focally “touching” the epidermis (Figure 4). Multinucleated giant cells, discrete edema within the granulomas, and dilated superficial vessels were also observed. PAS and Grocott stains were negative. Fite-Faraco stain did not show Mycobacteriae. Polymerase chain reaction (PCR) for Mycobacteriae was not performed. Enlarging plaque on the face with enlarged supraorbital nerve

"the spectrum is uninterrupted and there may be patients with an intermediate position among two groups" [5].
Anesthetic unilateral single lesions characterize TT leprosy, while bilateral asymmetrical distribution of lesions (macules, papules an plaques) characterize BT leprosy. Multiple symmetrically arranged macules and small or large nodules and plaques characterize BL and early LL. Loss of sensation is typical in TT and BT lesions, while it appears only late in BL and LL lesions. Early damage to autonomic nerve fibers impairs sweating and causes dry skin in TT and BT leprosy [1].
Leprosy reactions, divided into type 1 (called also reversal reaction or RR) and type 2 (called also erythema nodosum leprosum or ENL) reactions, are severe acute episodes that are common in immunologically unstable borderline patients, and involve an up-regulation of the host response to M. leprae antigens. RR is more frequent in BT patients during treatment and are due to an improvement of CMI against M. leprae (so-called upgrading RR) [1,7,8].
During RR, all three components of the peripheral nervous system are affected: sensory, motor and autonomic.
Routine laboratory investigations were within normal limits and an HIV test was negative. Chest X-ray was normal. Ophthalmological consultation was unremarkable.
Neurological consultation confirmed an enlargement of the supraorbital nerve without any neurological deficit. Magnetic resonance (MR) confirmed edema of the supraorbital nerve that was compressed at the frontal notch, explaining the origin of the unilateral headache and pain. A nerve biopsy was not performed.

Discussion
Leprosy or Hansen disease is a human chronic infectious disease associated with damaging inflammatory lesions in the skin and peripheral nerve caused by Mycobacterium leprae   Sensory loss causes anesthesia, analgesia and inability to discriminate hot and cold. Motor deficit causes muscle weakness, paralysis and atrophy with irreversible nerve damage, leading to impairments and permanent disability [1].
The most common nerves involved in RR are the median, radial and ulnar nerves, the sural, posterior tibial and perineal nerves, great auricular and the facial nerve. In all leprosy patients, accurate neurological examination includes testing for loss of sensation on skin lesions, palpation of commonly involved peripheral nerves, evaluation of sensory function, and muscular strength. When involved, nerves appear enlarged at palpation [1,2].
Nerve involvement can be confirmed using electrophysiology and echography or MR. RR has to be immediately treated with steroids before nerve damage occurs. Moreover, nerve involvement may be caused by compression due to edema, and the granulomatous inflammation affecting the nerve and can be treated surgically by opening the anatomic tunnel and performing an external neurolysis [1,9].
Concerning our patient, the clinical differential diagnosis included, among others, mainly sarcoidosis, skin lymphoma, granuloma annulare, tinea faciei, discoid lupus erythematosus and lupus vulgaris. A centrifugally enlarging anaesthetic plaque with dry skin in a subject coming from an endemic area favors leprosy. A single unilateral anesthetic lesion is typically seen in TT. The presence of multifocal epithelioid granulomas without necrosis but with perineural distribution confirmed leprosy and excluded tuberculosis and the other differential diagnosis. According to Ridley and Jopling the patient was classified as TT. The negative Fite-Faraco stain is not surprising because in more than 50% of TT patients M. leprae are not seen in TT biopsies because the CMI has already eliminated the pathogens. For the same reason, also PCR is unremarkable in more than 50% of TT patients, and it was not performed by us because a negative PCR does rule out the diagnosis [1,10].
The presence of multinucleated giant cells on histopathology, discrete edema within the granulomas, and dilated superficial vessels were histopathologic signs of RR [11], are compatible with the clinical enlargement of the supraorbital nerve and the headache reported by the patient. The supraorbital nerve is a branch of the frontal nerve, it is a pure sensitive nerve that is not frequently involved in leprosy. When enlarged it is palpable on the forehead slightly lateral to the midline. Its involvement produces minimal clinical damage to the patient. The supraorbital nerve can rarely cause headache and pain in the orbital cavity [1,12].
TT is a stable form of leprosy with a stable CMI against M. leprae. In contrast with borderline patients (BT, BB and BL), TT patients usually do not suffer from RR and do not shift to another form of the disease [1,8]. RR occurs more frequently in BT or BB and has been only rarely reported in TT