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CASE REPORT
Ahead of print publication  

Severe thrombocytopenia from acute levamisole toxicity in a Nigerian child


1 Departmet of Paediatrics, Federal Teaching Hospital, Gombe, Nigeria
2 Department of Paediatrics, Federal Medical Centre Nguru, Nguru, Nigeria
3 Department of Paediatrics, Cardiopulmonary Unit, Aminu Kano Teaching Hospital, Kano, Nigeria
4 Department of Paediatrics, Aminu Kano Teaching Hospital, Kano, Nigeria
5 Department of Paediatrics, Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria

Date of Submission11-May-2020
Date of Decision25-Aug-2020
Date of Acceptance20-Sep-2020

Correspondence Address:
Apollos Daniel,
Department of Paediatrics, Federal Teaching Hospital Gombe
Nigeria
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_251_20

  Abstract 


Levamisole-induced thrombocytopenia and vasculitis are rare entities in children. Here, we report a 5-year-old male who presented with complaints of purpuric rashes and nasal and gum bleeding for 24 h following intake of single high-dose levamisole for presumptive treatment of helminthiasis. No preceding symptoms of viral infection or bleeding into closed spaces were noted. He was clinically stable except for maculopapular and patchy purpuric rashes on the face, neck, and trunk. No hepatosplenomegaly or lymphadenopathy was observed. Full blood count and blood film showed severe thrombocytopenia of 6.00 × 109/L and platelets left shift with dysplastic neutrophils. He was commenced on prednisolone and transfused with fresh whole blood. The patient improved remarkably and showed reversal of hematological parameters within 48 h. Further, full blood count examination showed reactive thrombocytosis. Levamisole induces reversible thrombocytopenia by immune-mediated cytotoxic destruction of the platelets and white blood cells.

Keywords: Acute toxicity, bleeding, levamisole, maculopapular rash, thrombocytopenia



How to cite this URL:
Daniel A, Garba NA, Ahmadu I, Abubakar MS, Yejide OJ, Obiagwu P, Asani MO, Aliyu I. Severe thrombocytopenia from acute levamisole toxicity in a Nigerian child. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2021 Nov 30]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=319170




  Introduction Top


Levamisole is a heterocyclic aromatic compound belonging to the benzimidazole group. It is used as an antihelminthic and immunomodulatory agent in autoimmune disorders, such as rheumatic diseases and cancers. Levamisole restores normal immune response by stimulating macrophage chemotaxis and T-cell functions.[1],[2] Adverse reactions to levamisole include skin rashes from vasculitis, agranulocytosis, and thrombocytopenia. Thrombocytopenia is a rare but reversible blood dyscrasia occurring as an adverse effect of levamisole with intact bone marrow.[3]

Studies and case reports exist on levamisole-induced vasculitis and thrombocytopenia among chronic users of adulterated cocaine and adjuvant chemotherapy.[3],[4],[5] However, acute toxicity from single-dose intake of levamisole is a rare phenomenon in children. We therefore report severe thrombocytopenia following acute intake of overdose levamisole, which is the first occurrence to the best of our knowledge.


  Case Report Top


A 5 years old boy admitted with complaints of erythematous body rashes involving the face, neck, and trunk for a day duration. There was associated scanty nasal and gum bleeding for 5 h before presentation. There was no bleeding from other orifices, dizziness, or altered level of consciousness. No prior symptoms of the upper respiratory tract infection, fever, or joint/bone pain were observed. However, the patient was given an overdose of levamisole (4.2 mg/kg) for presumptive treatment of helminthiasis 24 h before onset of body rashes and bleeding.

On examination, he was a well-looking child with stable vital signs, except for maculopapular and patchy purpuric rashes involving the face, neck, trunk [Figure 1] and [Figure 2], and extremities. The largest rash located at the left iliac region measures 3–4 cm in its widest diameter. There were petechiae over the conjunctiva and gum. There was no lymphadenopathy, hepatosplenomegaly or conjuctival pallor.
Figure 1: Maculopapular purpuric rashes on the face and neck

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Figure 2: Left iliac purpuric patch

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Full blood count showed severe thrombocytopenia of 6.00 × 109/L, HGB of 11.4 g/dL, and white blood cells (WBC) of 8.44 × 109/L (neutrophils - 2.34 × 109/L and lymphocytes - 5.01 × 109/L). Blood film reported severe thrombocytopenia with left shift, neutrophils with dysplastic features, and normocytic, normochromic red cells. Clotting profile was normal. He was managed for levamisole overdose with severe thrombocytopenia. He received oral prednisolone 1 mg/kg/dose twice daily and transfusion with fresh whole blood. Repeat full blood count after 48 h showed increased in the platelets and neutrophils to 140 × 109/L and 3.50 × 109/L, respectively. He remained stable for 4 days without repeat nasal or gum bleeding, and the body rashes resolve completely. Further platelets count on follow-up visit after 2 weeks revealed thrombocytosis of 550 × 109/L.


  Discussion Top


Levamisole-associated serious adverse effects such as thrombocytopenia and neutropenia were reported in the 1970s, when it was used as an adjuvant chemotherapy and anti-inflammatory agent in chronic conditions.[3],[5] These adverse effects led to the withdrawal of the molecule from the United States market in 2000.[6] However, the drug is still use in off-label for antihelminthic and steroid-resistant nephrotic syndrome in resource-limited countries.[7]

The antihelminthic property of levamisole is due to its agonist effect on nicotinic acetylcholine receptors on the muscle cell of the helminths, which lead to paralysis and eventual death of the nematodes. It also inhibits degradation of stimulatory neurotransmitters and prolongs the duration of action, thus enhancing the psychotropic effects as it is used in cocaine adulterant.[1],[8] How levamisole cause thrombocytopenia is poorly understood. It has been suggested that the reactive thiol group has a haptens property that trigger immune-mediated cytotoxic response, leading to destruction of the platelets and WBC. The immune complexes also cause vasculitis with skin involvement that result into purpuric rashes, necrosis, or frank mucosal bleeding.[3],[4]

A systemic review[9] of levamisole-induced vasculopathy of 192 patients showed female preponderance with a mean age of 44 years (interquartile range of 38–50 years). The most commonly involved organ is the skin which manifests as purpuric rashes. A severe form of extensive skin necrosis leading to bilateral above-knee and nasal amputation has been reported in a chronic levamisole-adulterated cocaine user.[4] Our patient presented with skin rashes and thrombocytopenia following acute toxicity of levamisole. Thrombocytopenia is a rare and reversible adverse effect of levamisole as seen in the clinical presentation of our patient. Neurotoxicity presenting with ataxia has also been reported in a child following inadvertent administration of high-dose levamisole;[2],[10] however, this was absent in the index case.


  Conclusion Top


Levamisole acute toxicity is a rare phenomenon with varied manifestations in children. Thus, a high index of suspicion and detailed clinical history are required to unravel causes of rash in an apparently healthy child.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Martin RJ. Modes of action of anthelmintic drugs. Vet J 1997;154:11-34.  Back to cited text no. 1
    
2.
Winquist EW, Lassam NJ. Reversible thrombocytopenia with levamisole. Med Pediatr Oncol 1995;24:262-4.  Back to cited text no. 2
    
3.
Macfarlane DG, Bacon PA. Levamisole-induced vasculitis due to circulating immune complexes. Br Med J 1978;1:407-8.  Back to cited text no. 3
    
4.
Arora NP, Jain T, Bhanot R, Natesan SK. Levamisole-induced leukocytoclastic vasculitis and neutropenia in a patient with cocaine use: An extensive case with necrosis of skin, soft tissue, and cartilage. Addict Sci Clin Pract 2012;7:19.  Back to cited text no. 4
    
5.
Symoens J, Veys E, Mielants M, Pinals R. Adverse reactions to levamisole. Cancer Treat Rep 1978;62:1721-30.  Back to cited text no. 5
    
6.
Goyal A, Saul D, Annunziata G, Swami U. Choudhury M. “A self destructing reaction to a self destructive habit: Levamisole tainted cocaine causing autoimmune vasculitis.”New York J Med 2014;8:1-3.  Back to cited text no. 6
    
7.
Kalra S, Kanitkar M, Tiewosh K. Use of levamisole in children with nephritic syndrome: A retrospective study to examine its adverse effects in children with nephritic syndrome. J Mar Med Soc 2017;19:87-90.  Back to cited text no. 7
  [Full text]  
8.
Chang A, Osterloh J, Thomas J. Levamisole: A dangerous new cocaine adulterant. Clin Pharmacol Ther 2010;88:408-11.  Back to cited text no. 8
    
9.
Dartevel A, Chaigne B, Moachon L, Grenier F, Dupin N, Guillevin L, et al. Levamisole-induced vasculopathy: A systematic review. Semin Arthritis Rheum 2019;48:921-6.  Back to cited text no. 9
    
10.
Dubey AK, Gupta RK, Sharma RK. Levamisole induced ataxia. Indian Pediatr 2001;38:417-9.  Back to cited text no. 10
    


    Figures

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