This article is more than 5 years old. Information may no longer be current.
Brazilian man presents with bilateral madarosis
Click Here to Manage Email Alerts
A 30-year-old Brazilian man was referred by dermatology for an evaluation of bilateral total loss of eyebrow hair and eyelashes.
He had been living in the United States with his sister since 2002 and presented to the dermatology clinic at the urging of his sister for suspicious skin lesions. He first noted painless nodular skin lesions 5 years ago on his arms, legs and face. The nodules gradually became infiltrative and edematous on his face and were accompanied by progressive loss of eyebrow hair and eyelashes over the past 1 to 2 years. Within the year before presentation, he suffered recurrent burns to his forearms, hoarsening of his voice and nonproductive cough. He denied vision change, eye pain and headache. He reported no recent illness, coexisting medical condition or medication use. His family history was significant for similar signs and symptoms in his father.
The patient’s best corrected visual acuity was 20/25 with improvement on pinhole to 20/20 in both eyes. There was no afferent pupillary defect or anisocoria, and extraocular movements, confrontation visual fields and IOPs were all within normal limits. His external exam was notable for skin hyperpigmentation and diffusely indurated skin, most markedly on his brow, nose and ears. He had symmetrically distributed skin nodules on his face, which were non-tender to palpation. He had a slight saddle nose deformity. He had near complete loss of eyebrow hair and eyelashes (Figure 1). Cranial nerves V and VII were intact.
On slit lamp biomicroscopy, he had trace conjunctival injection in both eyes. He had superior corneal haze with multiple white superficial punctate opacities and round subepithelial infiltrates in both eyes, more extensive in the left eye than the right (Figure 2). The remainder of the anterior segment exam was within normal limits, and the dilated fundus exam was unremarkable.
A physical exam revealed multiple non-tender nodules on the patient’s trunk, arms and legs. He also had multiple small, tender red nodules on his left upper arm and across his upper back. He had mild edema of his face, mild pedal edema of both feet up to his mid-tibia and mild edema of both hands. He had mild tenderness to palpation over the left ulnar nerve, and multiple burn scars on the left third finger and left forearm. He had a non-erythematous ulcer on the right third toe distally. There were no focal neurological findings. The referring dermatologist had previously obtained a CBC, metabolic panel, Strongyloides antibody, hepatitis panel, Quantiferon gold, G6PD, HIV, Chagas antibody and chest X-ray, which were all unremarkable.
Figure 1. External photo reveals small coalescent infiltrative nodules of the face, most notable across the brow and nasolabial folds, with induration and prominence across the brow, slight saddle nose deformity and bilateral madarosis.
Images: Klein K, Soukiasian SH
Figure 2. Slit lamp photo of the left eye shows small, round, white subepithelial infiltrates across the superior cornea with scattered punctate epithelial opacities. The infiltrates most likely represent bacilli phagocytosed by macrophages, or “lepromas.”
What is your diagnosis?
Madarosis, skin lesions
The diagnosis of leprosy, or Hansen’s disease, can be made clinically by recognition of characteristic features and confirmed by skin histopathology. According to the World Health Organization, a patient with Hansen’s disease has one or more of the following features: hypopigmented or reddish skin lesions with loss of sensation, involvement of the peripheral nerves as demonstrated by thickening accompanied by loss of sensation, or skin smear positive for acid fast bacilli. Skin biopsies should be full dermal thickness, taken from an active edge of a lesion and stained using a Fite stain to demonstrate acid-fast bacilli and granulomatous disease.
The patient’s left wrist skin biopsy was positive for Mycobacterium leprae using a Fite stain and showed numerous organisms, consistent with the diagnosis of lepromatous leprosy.
A differential diagnosis for madarosis is broad and ranges from common conditions such as blepharitis, atopic dermatitis, seborrheic dermatitis, psoriasis and telogen effluvium to less common systemic conditions such as sarcoidosis, discoid lupus erythematosus, scleroderma, leprosy, thyroid disease and syphilis. The differential diagnosis of madarosis accompanied by corneal infiltrates is more limited and includes mycosis fungoides, sarcoidosis, systemic lupus erythematosus and ocular tuberculosis.
Discussion
It has been reported that leprosy has the highest incidence of ocular involvement of any human bacterial infection, and it represents a major cause of blindness in developing countries worldwide. There are three clinical forms of leprosy: lepromatous or nodular leprosy, which is characterized by poor cell-mediated immunity and extensive infiltration with acid fast Mycobacterium leprae bacilli; tuberculoid leprosy, which is characterized by intact cell-mediated immunity and few to no acid fast bacilli in tissues; and an intermediate or borderline leprosy, which combines features of the other two forms.
The eye is involved in up to 6% to 90% of leprosy cases, and blindness occurs in 5% to 14% of cases. Ocular lesions are seen more frequently with increased age and duration of disease, and they are more common in lepromatous or multibacillary leprosy. Ocular complications result from primary infection of the eye and accumulation of bacilli in ocular tissues, with secondary damage due to neural involvement and acute inflammation.
Madarosis is the hallmark of lepromatous leprosy and is characteristically a bilateral symmetric scarring loss of lashes due to infiltration of hair follicles, although it typically takes 5 to 10 years of untreated infection before manifesting. Absence of madarosis is a good prognostic sign for the extent of disease.
Corneal disease is also common in leprosy. Lagophthalmos typically presents early, occurs secondary to infiltration and damage to the seventh nerve, and is the primary factor contributing to corneal disease. Inflammatory damage to the fifth nerve can lead to decreased corneal sensation. Additionally, primary infection of the cornea by the bacilli results in punctate keratitis and corneal stromal infiltration by macrophages that phagocytose bacilli and form small “lepromas” in the superficial stroma, which are often noted in the superior cornea. Furthermore, involvement of the lacrimal system can impair tear production and drainage. Alone or together, these factors ultimately result in corneal microtrauma, exposure keratitis, secondary infections, opacification and blindness.
After the cornea, the iris is the structure most commonly affected in the form of a chronic anterior uveitis. The pathophysiology is poorly understood and is likely a result of low-grade inflammation secondary to bacterial invasion of the iris ciliary body and anterior chamber coupled with a type 2 immunocomplex deposition reaction. Uveitis is found most commonly in multi-bacillary patients; eyes are usually quiet with occasional subacute episodes that may go unnoticed or untreated for years. Over time, the inflammation leads to iris atrophy, miosis and cataract, the latter two of which can also contribute to severe vision loss.
Systemic treatment of leprosy depends upon the histopathologic form of the disease. Current treatment recommendations are often based on the World Health Organization treatment regimens of multi-drug therapy that were put forth in the 1980s after resistance emerged with the use of dapsone monotherapy. In accordance with WHO guidelines, our patient was treated with triple therapy consisting of daily clofazimine, rifampin and dapsone. In addition, pentoxifylline and prednisone was added for treatment of neuritis and erythema nodosum. In addition, the ophthalmologist can treat lagophthalmos and corneal exposure with education to inspect the cornea for foreign bodies, increased blink rate and surgical correction, if necessary. Acute uveitic episodes should be treated with cycloplegia and steroids, and chronic or subacute episodes are managed with topical corticosteroids and NSAIDs. Complicated cataracts should be removed surgically after inflammation is properly controlled.
Although Hansen’s disease is an important cause of blindness worldwide, the diagnosis is often missed by ophthalmologists in developed countries due to its rarity and lack of disease awareness. The majority of patients encountered are from endemic areas. With increased travel and globalization, ophthalmologists need to have heightened awareness of these characteristic symptoms. The ophthalmologist may be the first clinician to see a patient with leprosy because of complications resulting from ocular infiltration and exposure. The inclusion of Hansen’s disease on an ophthalmologist’s differential diagnosis is key to timely diagnosis and treatment and ultimately the prevention of blindness.