Painful lesions with fever and malaise - Clinical Advisor

Painful lesions with fever and malaise

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A 45-year-old man presents with fever, malaise, and painful patches, plaques, and nodules on the face, trunk, and upper and lower extremities. He emigrated from Burma a few months ago and is staying with family. He states that no other individual living with him has similar symptoms. On examination, the patient has a temperature of 100.7 degrees Fahrenheit, but his vital signs are otherwise stable. He has scattered tender, pink-to-violaceous nodules, patches, and plaques most prominently seen on the ears and extremities but also scattered over the face and trunk. A neurologic examination demonstrates that sensation is intact and there are no tender or enlarged peripheral nerves. 


Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. Infection by these mycobacteria often involve the skin and nerves, which can ultimately lead to deforming, disabling, and stigmatizing disease.Today, leprosy is endemic in tropical...

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Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae. Infection by these mycobacteria often involve the skin and nerves, which can ultimately lead to deforming, disabling, and stigmatizing disease.

Today, leprosy is endemic in tropical and subtropical areas such as Central and South America, Africa, and Asia. In the 1980s, there was an estimated 11 million to 15 million people worldwide with leprosy. By 2010, there was an estimated 250,000 cases per year.1 In the United States, most cases are imported, but a small fraction of cases are endemic in the southeastern region of the United States and in Hawaii, possibly due to exposure to armadillos.2

Leprosy spreads when there is a contagious patient, a susceptible patient, and close or intimate contact. There is an estimated 25% risk of acquiring the disease from household contacts.1 This bacillus spreads predominantly through nasal and oral droplets or less often, through eroded skin.1,2 Of note, there could still be viable bacilli in dried secretions for up to 7 days. However, approximately 90% of exposed individuals never develop the disease.2

This variance in development of the disease may be due to genetic susceptibilities. For example, it is hypothesized that individuals with human leukocyte antigen (HLA)-DR2 and HLA-DR3 genes are more likely to develop the tuberculoid form of leprosy, whereas those carrying the HLA-DQ1 gene develop the lepromatous form of leprosy.1 In addition, correlations have been found between leprosy and the parkin RBR E3 ubiquitin protein ligase (PARK2) gene and the lymphotoxin-alpha gene, which are also associated with the development of Parkinson’s disease and malaria parasitemia, respectively.2,3

M. leprae is a small, weakly acid-fast, obligate, intracellular rod bacterium that tends to colonize macrophages and Schwann cells. The peripheral nerves, mucous membranes, skin, bones, and viscera are often the most likely areas that are involved. Interestingly, these mycobacteria thrive in cooler regions of the body, such as the nose, testicles, ear lobes, and superficial peripheral nerves in the skin.1,2

If untreated, lepromatous leprosy will continue to progress and cause deforming and disabling symptoms. Patients in advanced stages of the disease can demonstrate madarosis, or loss of hair from the outer third of the eyebrows, leonine facies, saddle nose, infiltration of bilateral earlobes, acquired ichthyosis of the lower extremities, gynecomastia, papal and claw hand due to flexion contractures, orchitis leading to sterility, neurotrophic ulcers, foot drop, and hammer toes. 


A rare complication known as Lucio’s phenomenon can occur in diffuse lepromatous leprosy, where purpuric macules evolve into bullae that subsequently ulcerate. This phenomenon is also associated with fever, splenomegaly, glomerulonephritis, hypoalbuminemia, hypocalcemia, polyclonal gammopathy, and anemia.1-3 These lesions are quite painful and often occur below the knees. Biopsy of these lesions will show organisms teeming not only in the skin but also within blood vessels.2

Although lepromatous leprosy often does not have initial nervous system involvement, neuropathy in a symmetric stocking glove distribution will eventually develop if untreated. Debilitating ocular involvement can lead to lagophthalmos (ie, inability to close eyes), keratitis, episcleritis, corneal and conjunctival anesthesia, and eventual blindness.1,2,4,5

Lepromatous leprosy may present on a broad clinical spectrum based on immunologic response or resistance. The patient in our case had the lepromatous type of leprosy that represents the multibacillary end of the spectrum due to depressed cell-mediated immunity. On the other hand, tuberculoid leprosy represents a strong immunologic response that leads to few or no organisms in the lesions of patients who have the condition. 


Lepromatous leprosy can be differentiated from tuberculoid leprosy by clinical presentation. The lepromatous form often presents with numerous macules, papules, and nodules in a symmetric distribution without loss of sensation or nerve involvement.1,2,4,5 A biopsy of these skin lesions would demonstrate many of these organisms as globi on histopathology.1

On the other hand, patients with tuberculoid leprosy often have asymmetric, well-demarcated, infiltrative plaques with some loss of sensation due to nerve inflammation or destruction leading to anesthetic areas. Biopsy of these skin lesions would demonstrate few organisms, if any. Furthermore, peripheral nerves can become enlarged and palpable and are important in physical examination. 


Between these two extremes, there are many permutations in clinical presentation, constituting the borderline spectrum.1,4,5 Borderline disease is often known to be unstable and moves over time from the tuberculoid end of the spectrum toward the lepromatous end. This is a process known as downgrading.1-2,4-5

Differential diagnoses for lesions as seen in the patient in our case may include mycosis fungoides, leishmaniasis, syphilis, sarcoidosis, cellulitis, erythema nodosum, and cutaneous tuberculosis. Nerve involvement may be mistaken as a peripheral neuropathy that is secondary to diabetes, nutritional deficiencies, vasculitis, syringomyelia, and poliomyelitis.1-2,4-5

Ideally, a punch biopsy should be performed down to the subcutaneous fat over an active border of one of the lesions. A Fite stain often can help accentuate these acid-fast bacilli.1-2,4-5 It is important to note that M. leprae cannot be cultured, and polymerase chain reaction testing has not been very useful due to lack of sensitivity.2

Since multidrug therapy is extremely effective and this patient had lepromatous leprosy, a regimen of 3 drugs was initiated: rifampin at 600 mg by mouth every month; clofazimine at 300 mg by mouth each month and 50 mg by mouth every day; and dapsone at 100 mg by mouth daily.1 The regimen was planned for 1 to 2 years,1 followed by observation for 5 years. However, the patient then developed fever, myalgia, joint swelling, and nodular skin lesions that were thought to be due to a treatment-induced type-2 skin reaction called erythema nodosum leprosum. Therapy with thalidomide at 200 mg by mouth every day was initiated.1-2,4-5 The patient’s lesions eventually resolved completely, but he will need long-term suppressive therapy and follow-up.

Tiffany Shih, MD, is a resident physician at the University of Minnesota in Minneapolis.


References 


  1. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2012:1221-1228.
  2. James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: 
Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2011:
334-344.
  3. Rodrigues LC and Lockwood DNj. Leprosy now: Epidemiology, 
progress, challenges, and research gaps. Lancet Infect Dis. 2011;11(6):
464-470.
  4. Moschella SL. An update on the diagnosis and treatment of leprosy. J Am Acad Dermatol. 2004;51(3):417-426.
  5. Eichelmann K, González González SE, Salas-Alanis JC, Ocampo-Candiani J. Leprosy. An update: Definition, pathogenesis, classification, diagnosis, and treatment. Actas dermo-sifiliográficas. 2013; 104(7):554-563.
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