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A case of erythema nodosum leprosum reaction with diffuse alveolar haemorrhage, successfully treated by pulsed methylprednisolone.


Diffuse alveolar haemorrhage (DAH) is a life-threatening condition. Although a variety of etiologies could predispose to the development of DAH, erythema nodosum leprosum (ENL) has in the past never been described as a cause. ENL is a Type 2 reactional leprosy and commonly occurs in borderline leprosy and lepromatous leprosy. (1) Because ENL is an immune-complex mediated disease, the clinical features could, therefore, be present in the involvement of multiple organ systems and include such diseases as polyarthritis, myositis, neuritis, iridocyclitis and lymphadenitis. (2-3) In this report we present a case of ENL with DAH which was successfully treated by pulsed methyprednisolone.

Case Report

An 18 year old man was admitted with complaints of multiple enlarged painful subcutaneous nodules for the past month, a low grade fever, a loss of 6 kg of body weight during the preceding 3 months and arthralgia. The patient had no known exposure to tuberculosis and was not taking any drugs prior to visiting our hospital. On examination the patient had a low grade fever, multiple cervical lymphadenopathy, mild hepatosplenomegaly and polyarthritis in his knees, elbows, wrists and fingers. He had multiple discrete symmetrical, ill-defined, painful erythematous dermal and subcutaneous nodules on top of crusted ulcers and infiltrative erythematous plaque over his face, upper trunk and limbs (Figure 1).


There was no thickening of the peripheral nerves, sensory loss or muscular weakness. A skin biopsy was performed from the right forearm lesions. Serial haematology and clinical chemistry were performed (Table 1).

The urine analysis was negative. The abdominal ultrasonography revealed mild hepatosplenomegaly and the chest radiography showed normal findings.

At 24 hours after admission, the patient suddenly developed massive haemoptysis with severe hypoxia, along with a new-onset anemia (hemoglobin level, 8-8 g/dL) compared to the hospital admission value of 13-3 g/dL (Table 1). A physical examination of the chest revealed bilateral late, fine, inspiratory crackles in the lower lung fields. The chest radiography revealed bilaterally diffuse alveolar opacities (Figure 2A).

The patient needed intubation and mechanical ventilation. The provisional diagnosis was suggestive of alveolar pulmonary haemorrhage.

Approximately 72 hours later, the patient continued to have worsening haemoptysis and a repeat chest radiography showed progressive bilateral alveolar infiltrations. There was no growth of pathogenic bacteria or evidence of fungal infection in the blood and bronchial fluid. The Ziehl-Neelsen acid-fast stains on the sputum also were negative. The test results for the immunological tests are shown in Table 2.

A skin biopsy revealed diffuse nodular infiltration of numerous foamy histiocytes, lympho-histiocytes and giant cells with clumps of fragment bacilli (globi) within the few foamy cells, including predominant polymorphic neutrophil infiltration throughout the dermis (Figures 3A and 3B).

Scanty granular bacilli were found by Wade-Fite staining and these findings were compatible with erythema nodosum leprosum (Figure 4).


The slit skin smear was not performed. The patient was conclusively diagnosed with ENL with diffuse alveolar haemorrhage.

Thereafter, he was administered 1 gm of intravenous methylprednisolone daily for 3 days. The patient's pulmonary symptoms improved dramatically after the second dose of pulse corticosteroids. The repeated chest radiography after 3 days of pulse therapy showed the resolution of opacities (Figure 2B).

As a result, the corticosteroid was switched to oral prednisolone (1 mg/kg/day) combined with multibacillary multi-drug therapy (MB-MDT) which consisted of a monthly dose of 600 mg rifampicin and 300 mg clofazimine and a daily dose of 100 mg dapsone and 50 mg clofazimine for 1 year. The prednisolone was tapered off, 5-10mg every 4 weeks over 6 months. There was no growth of Mycobacterium tuberculosis in his blood or sputum after 3 months of incubation. The patient completed a follow-up check, which showed a clearance of all symptoms and that he was clinically well. The follow-up slit skin smears from routine sites showed negative findings.


This report describes a highly unusual event of diffuse alveolar haemorrhage (DAH) developing in association with erythema nodosum leprosum (ENL). Many causes of DAH have been described to have pulmonary capillaritis that include systemic vasculitis, collagen vascular diseases, antiphospholipid syndrome, Gooodpasture's syndrome and Behcet's syndrome, (4) whereas ENL has not been previously described as a cause. Because DAH has a variety of pathogenic mechanisms, establishing the diagnosis should be confirmed by the histopathology of samples obtained by bronchoscope or of bronchoalveolar larvage. (4) Unfortunately, we did not have a bronchoscope available, thus the diagnosis of DAH in our patient is purely clinical and not proven. In our case, we needed to exclude a possible cause of DAH, particularly systemic vasculitis such as SLE, small vessel vasculitis, antiphospholipid syndrome, and other autoimmune disease including infectious diseases. However, our case was absence of the characteristic clinical features of such diseases as well as the negative specific autoantibodies including antinuclear antibody, antineutrophilic cytoplasmic antibody, anti-dsDNA, rheumatoid factor and anti-cardiolipin, which are of benefit in making the diagnosis. (4) We were unable to investigate any antibodies, including anti-glomerular basement membrane, because of the limitations in our ability.


The skin lesions, skin smear and pathological features are useful for the diagnosis of leprosy, classifying the type and deciding on the appropriate treatment. Unfortunately, we did not perform a slit skin smear on our patient because of the life-threatening situation. Therefore, ENL was consequently diagnosed on the basis of the clinical features and the pathological findings of the skin biopsy. Even though the evidence of a skin smear and the clinical of leprosy have been limited, our patient was presenting features of multibacillary leprosy according to the Ridley-Jopling classification. Moreover, our patient also has to be clinically considered in the differential diagnosis of other diseases that present with symptoms of tender nodules, such as erythema nodosum, other panniculitides, Sweet syndrome, and nodular vasculitis. However, histological findings are helpful for a definite diagnosis.


It is not known whether the association between ENL and DAH is coincidental or whether there is some common pathogenic link. Several studies have postulated that ENL is an immune-complex mediated process resulting in the overproduction of immunoglobulin, complement and cytokines, whereas DAH is described by pulmonary capillaritis as a result of the deposition of immune-complexes leading to an inflammatory cascade, finally followed by alveolar hemorrhage. (2-9) Based on these observations, we speculate that the immune-complex mediated process in ENL may have played an important role in the development of DAH. Thus, we suggest that the demonstration of immune-complex deposition in lung specimens by immunofluorescent microscopy would be beneficial for a definitive diagnosis of this entity.

Diffuse alveolar haemorrhage is a life-threatening condition with a high mortality; a patient needs prompt diagnosis and aggressive management steps in treatment. Whereas, the occurrence of DAH with ENL has not been previously proposed, the data on treating this condition is limited. Because we speculated that the immune-complex mediated process may have played an important role in the development of DAH in ENL, corticosteroid should be a useful treatment. Our patient was therefore administered pulse methylprednisolone and he responded well to this regimen. However, corticosteroid is also the mainstay of management in ENL and pulmonary capillaralitis causing DAH. (4,5)

In conclusion, this case report highlights the rare occurrence of diffuse alveolar hemorrhage in ENL. Such a case illustrates that the immune-complex process may play an important role in the pathogenesis of DAH and that intravenous administration of a high dose corticorsteriod may be beneficial for an ENL patient with DAH. The diagnosis of DAH is unclear and needs to be confirmed by histopathology to the find the possible cause.


The authors wish to thank Associated Professor Sauvarat Auepemkiate, Department of Pathology, Faculty of Medicine, Prince of Songkha University and Dr. Walaiorn Pratchyapruit, Institute of dermatology, Ministry of Public Health, for their kindness in performing the histological examination of the skin biopsy specimen mentioned in this paper.


(1) Kumar B, Dogra S, Kaur I. Epidemiological characteristics of leprosy reactions: 15 years experience from north India. Int J Lepr Other Mycobact Dis, 2004; 72: 125-133.

(2) Wemambu SNC, Turk JL, Waters MFR, Rees RJW. Erythema nodosum leprosum: a clinical manifestation of the arthus phenomenon. Lancet, 1969; 2: 933-935.

(3) Cuevas J, Rodriguez-Peralto JL, Carrillo R, Contreras F. Erythema nodosum leprosum: reactional leprosy. Semin Cutan Med Surg, 2007; 26: 126-130.

(4) Green RJ, Ruoss SJ, Kraft SA et al. Pulmonary capillaritis and alveolar hemorrhage update on diagnosis and management. Chest, 1996; 110: 1305-1316.

(5) Marlowe SNS, Lockwood DNJ. Update on leprosy. Hosp Med, 2001; 62: 471-476.

(6) Sheagren JN, Block JB, Trautman JR, Wolff SM. Immunologic reactivity in patients with leprosy. Ann Intern Med, 1969; 70: 295-302.

(7) Rao TD, Rao PR. Serum immune complexes in erythema nodosum leprosum reactions of leprosy. Indian J Lepr, 1988; 60: 189-195.

(8) Moran CJ, Ryder G, Turk JL, Waters MF. Evidence for circulating immune complexes in lepromatous leprosy. Lancet, 1972; 16: 572-573.

(9) Lahiri R, Sandoval FG, Krahenbuhl JL, Shannon EJ. Activation of complement by mycobacterium leprae requires disruption of the bacilli. Lepr Rev, 2008; 79: 311-314.

NARONGWIT NAKWAN, Department of Medicine, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, Thailand

SUNISA THAICHINDA, Division of dermatology, Department of Medicine, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, Thailand

NARONGSAK NAKWAN, Department of Pediatrics, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, Thailand

Accepted for publication 27 June 2010

Correspondence to: Narongwit Nakwan, M.D, Department of Medicine, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, Thailand 90110 (Tel: + 66 8 1898 4566; Fax: + 667 4411333; e-mail:
Table 1. Monitoring of haematologic and clinical
chemistry laboratory values during admission

                                                   72 hours

                                 24 hours later    Started
                                 Presented with    pulse
Period of            Admission   acute dyspnea     methypred-
treatment            date        and haemoptysis   nisolone

Haemoglobin (g/dL)       13.3               8.8          8.8
Hematocrit (%)             40              25.9         25.9
Total WBC count        12 000            19 300       19 300
  (x 109/L)
Neutrophils (%)            70                68           90
Lymphocytes (%)            25                22            6
Monocytes (%)               3                 6            2
Eosinophils (%)             2                 4            2
Platelet counts
  (x 109/L)           196,000           288,000      288,000
Prothrombin time           14                13          13.5
  (10-5-13-5 sec)
International            1.14              1.12         1.13
  ratio (1-1.3)
  time                     30                28          27.5
  (22-8-31 sec)
SGPT (10-30IU/L)           10                28           25
SGOT (9-43 IU/L)           12                40           38
Alkaline                  110               112          102
Total serum
  bilirubin (mg/dL)        0.7               0.6          0.8
Blood urea
  nitrogen (mg/dL)         10                14           12
Creatinine (mg/dL)         0.8               1.0          0.9
Erythrocyte               140
  rate (mm/hr)

                     5 days

Period of            pulse        2 weeks
treatment            methypred-   later

Haemoglobin (g/dL)          13        12
Hematocrit (%)              38        37
Total WBC count         12 500    11 000
  (x 109/L)
Neutrophils (%)             75        70
Lymphocytes (%)             23        25
Monocytes (%)                3         2
Eosinophils (%)              2         3
Platelet counts
  (x 109/L)            275,000    188,000
Prothrombin time
  (10-5-13-5 sec)
  ratio (1-1.3)
  (22-8-31 sec)
SGPT (10-30IU/L)
SGOT (9-43 IU/L)
Total serum
  bilirubin (mg/dL)
Blood urea
  nitrogen (mg/dL)
Creatinine (mg/dL)
  rate (mm/hr)

Table 2. Results of immunologic
tests on admission

Test                             Result

Anti-HIV antibody                Negative
Anti-HCV antibody                Negative
HBs Ag                           Negative
Anti-streptolysin-O              Negative
Antinuclear antibody             Negative
Anti-dsDNA antibody              Negative
Rheumatiod factor                Negative
Antineutrophil cytoplasmic       Negative
Leptospira antibody              Negative
Serum C3 (75-135mg/dL)           98
Serum C4 (10-40 mg/mL)           24
C-reactive protein (4-6 mg/L)    24.6
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Title Annotation:CASE REPORT
Author:Nakwan, Narongwit; Thaichinda, Sunisa; Nakwan, Narongsak
Publication:Leprosy Review
Date:Jun 1, 2010
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