University of Alabama at Birmingham 2007 Case #9 Universidad Peruana Cayetano Heredia

During the past week the Gorgas Course in Clinical Tropical Medicine concluded with a 4-day field trip to Iquitos on the banks of the Amazon River.  Iquitos, with a population of approximately 500,000, is the largest city in the world that is reachable only by air and by river.  The nearest road ends over 400 km away.  The following case was seen in the outpatient department of the Iquitos Hospital in Iquitos, Peru.  We thank Dr. Pedro Legua from our institute for his advice on this patient.

Publishing a case report for 9 consecutive weeks would not be possible without the assistance of an extremely dedicated group of people.  We would like to thank in particular: Dr. Carlos Seas, Clinical Rounds Coordinator for the Gorgas Courses for case selection, coordination of case summaries and images; Drs. Jaime Cok and Juan Ferrufino for preparation and discussion of pathologic specimens, and Adam Plier of the UAB Center for Geographic Medicine for all publishing on the Gorgas Course web site.

We hope you have enjoyed this year’s cases.  In August 2007 we will be running the 2-week Gorgas Expert Course and will present 2 more cases during that time.  We will also be in touch in February 2008 at the beginning of next year’s case series.

These cases will be re-formatted to meet CME guidelines and will be available for online CME credit later this year.  We look forward to providing more cases during the 2008 Gorgas Course.

Please send any suggestions or comments for these cases to info@gorgas.org.

David O. Freedman & Eduardo Gotuzzo
Course Directors

History:  Male patient, 47 years old, lives in the jungle, worked in agricultural activities.  First manifest his illness at age 14 with numbness on the dorsal aspect of his right foot and on the lateral aspect of the right leg.  At age 17 he noticed “hypopigmented macules” on his trunk that had reduced sensation.  At age 23 years there was pain in the nerves of both arms that curled the fingers of both hands.  He never sought medical attention but took herbal remedies.  At age 26 years there was edema of the ankles and pain in the internal aspect of both ankles, and then the toes of both feet curled.  Since the age of 30 years old he has had recurrent episodes of erythematous painful nodules in the skin all over his body.  In the last year he has noticed swelling of his face and earlobes.

Epidemiology:  Lifelong resident of a remote area of the jungle in the Loreto department.  No contact with anyone with a similar illness.

Physical Examination:  Afebrile.  Infiltrative diffuse lesions of the skin of his forehead, malar areas, cheeks, nose and chin, with loss of eyebrows and eyelashes present [Image A].  In addition, the infiltrative lesions of the ear had overlying ulceration [Image B].  The skin of his trunk and limbs had numerous tender erythematous nodules of varying sizes from 1 to 1.5 cm in diameter and several papules (note right arm, Image C).  There was mild enlargement of both ulnar nerves, more marked on the left side; of both common peroneal nerves, more marked on the left side; and of both posterior tibial nerves.  There was bilateral glove and stocking anesthesia with loss of sensation to the elbows and mid-calf.  There was bilateral corneal anesthesia (loss of blink reflex as tested with a wet tissue, Image D).  There was complete clawing of all digits on both hands with cutaneous ulceration, loss of tissue, bone resorption, and loss of the fifth finger of the right hand [Image E].  Similar changes on feet, and plantar ulcers on the left foot [Image F, G].

Laboratory Examination:  Diagnostic material was obtained from the earlobes.

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Diagnosis:  Erythema nodosum leprosum.  Lepromatous leprosy due to Mycobacterium leprae.

Discussion: With this classic clinical picture and with limited resources, the clinical picture in this patient would provide a definitive diagnosis [reviewed in Lancet. 2004 Apr 10;363(9416):1209-19. and Br Med Bull. 2006;77-78:103-121.].

In this patient, we did obtain slit skin smears stained for acid-fast bacilli with the following results: 5+ from the right earlobe, 5+ from the left earlobe.  Slit skin smears are performed by making small (5 mm length, 2 mm depth) slits in pinched skin (to avoid bleeding), the edges of which are scraped.  The material obtained is smeared on a clean slide and stained for AFB.  Generally ear lobes, elbows, and knees are examined.  The bacterial index ranges from zero (no bacilli in 100 oil-immersion fields) to 6+ (over 1000 bacilli in one field).

The usual and most practical grading system is the WHO classification.  For therapeutic purposes, it matters only whether the patient has paucibacillary or multibacillary disease.  Where no slit skins smears can be done, paucibacillary leprosy is defined as five or fewer skin lesions; multibacillary cases have six or more lesions.  Paucibacillary disease usually presents with small numbers of hypopigmented macules or erythematous plaques with absent or reduced sensation, well-demarcated borders and some scaliness.  Multibacillary disease is usually widespread at diagnosis with multiple plaques or infiltrated areas of skin with indistinct borders, non-anesthetic, and papules or nodules.  The disease can be classified precisely in the immunologic sense using the traditional Ridley-Jopling classification.  This is a spectrum of disease ranging from tuberculoid leprosy (TT) with no or few AFB in lesions and good cell mediated immunity, to lepromatous leprosy (LL) with many AFB and poor cell-mediated immunity.

Leprosy is a disease of peripheral nerves and skin.  Leprosy can be diagnosed clinically in any patient with simultaneous skin lesions and sensory loss over the lesions unless there is hyperkeratosis.  This unfortunate patient with a 33-year history of undiagnosed and untreated disease presents together many of the advanced clinical lesions of end stage disease including the facies and pattern of infiltrative skin lesions.  Peripheral nerves such as the ulnar, median, common peroneal, posterior tibial, facial, and greater auricular are often palpably enlarged.  In advanced neuropathy this leads to motor deformities such as claw hand, footdrop, claw toes, and hand and foot insensitivity.  Motor nerve paralysis and longstanding sensory neuropathy of the glove and stocking variety, as in this patient, results in deformities of the hands and feet, abnormal pressure, ulceration due to burns and other daily trauma that is unnoticed by the patient.  Infection of bone marrow of phalanges by leprosy bacilli results in osteoporosis, fractures, bone resorption and shortening of digits.  The corneal anesthesia and subsequent trauma due to unnoticed foreign bodies may lead to eventual blindness.

Type 2 reaction, the most common presentation of which is erythema nodosum leprosum (ENL), is a systemic immune mediated disorder, usually with high levels of tissue and circulating TNF-alpha. ENL presents with fever together with many tender erythematous nodules that occurs in up to 50% of lepromatous leprosy cases [Am J Trop Med Hyg. 2006;74(5):868-79.] due to their high bacterial loads and in about 10% of those with borderline lepromatous disease.  ENL may also produce to varying degrees, neuritis, edema, arthralgias, leukocytosis, uveitis, dactylitis, periostitis, orchitis, and nephritis.  ENL may occur in patients prior to therapy, during therapy and/or after therapy until the antigen load decreases markedly.  ENL may be chronic and ongoing or may present as repeated acute episodes.

Image H for 03/30/07The standard WHO regimen for paucibacillary disease is 100 mg Dapsone a day unsupervised and 600 mg Rifampin once per month directly observed for 6 months.  For multibacillary disease patients receive 100 mg Dapsone and 50 mg Clofazimine a day unsupervised and 600 mg Rifampin and 300 mg of Clofazimine directly observed once per month.  A standard WHO multibacillary dose-pack is shown [Image H]; the instructions in English must be clarified for all healthcare staff and patients.  WHO now recommends only 1 year of therapy for multibacillary cases [controversy discussed in Lancet 2004 Apr 10;363(9416):1209-19], but some would treat those with high bacterial indices (4 to 6+) for the previously recommended 2 years due to higher relapse rates.  A myriad of treatment reactions can occur, the possibility of which should be informed and explained to the patient before starting treatment and a reference text should be consulted prior to initiation of therapy by anyone not familiar with these.

ENL can be treated symptomatically if mild or with prednisone, clofazimine, or thalidomide if severe.  Thalidomide is the drug of choice for severe ENL and also very effective for neuritis due to type 2 reaction.  A dose of 300 to 400 mg daily will usually control the reaction within 48 hours.  The dose is then tapered to a maintenance level, which is generally around 100 mg daily; every few months attempts are made to taper off the drug.  Thalidomide is currently unavailable in Peru.  Prednisone is generally indicated if neuritis is present but generally requires prolonged therapy and patients are difficult to wean.  Prednisone therapy needs ongoing medical supervision and would be extremely difficult to manage in this impoverished nation