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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 7  |  Issue : 2  |  Page : 84-87

Lenalidomide in a case of thalidomide intolerant erythema nodosum leprosum


Department of Dermatology, INHS Asvini, Mumbai, Maharashtra, India

Date of Submission01-Aug-2020
Date of Decision19-May-2021
Date of Acceptance01-Sep-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Jandhyala Sridhar
Department of Dermatology, INHS Asvini, Colaba, Mumbai 400005, Maharashtra.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_50_20

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  Abstract 

Lenalidomide is an immunomodulatory drug, which is considered to be a derivative of thalidomide. It has a more potent suppressive effect on tumor necrosis factor-α (TNF-α) production and has a more tolerable adverse effect profile as compared to its parent drug. It has been approved by FDA for use in multiple hematopoietic malignancies and myelodysplasia, but unlike thalidomide its use in erythema nodosum leprosum (ENL) has not been reported so far. Herein we report a case of 45-year-old man with Hansen’s disease (BL) on MDT for 4 months who presented with ENL and was managed with minimum dose of lenalidomide.

Keywords: Erythema nodosum leprosum, lenalidomide, thalidomide intolerance


How to cite this article:
Chahar SL, Mani S, Sridhar J, Srinivasan P. Lenalidomide in a case of thalidomide intolerant erythema nodosum leprosum. Indian J Drugs Dermatol 2021;7:84-7

How to cite this URL:
Chahar SL, Mani S, Sridhar J, Srinivasan P. Lenalidomide in a case of thalidomide intolerant erythema nodosum leprosum. Indian J Drugs Dermatol [serial online] 2021 [cited 2024 Mar 29];7:84-7. Available from: https://www.ijdd.in/text.asp?2021/7/2/84/332425




  Introduction Top


Lenalidomide is an immunomodulatory drug, which has been approved by FDA for use in multiple conditions such as multiple myeloma, myelodysplastic syndrome, marginal zone lymphoma to name a few. It is considered to be a derivative of thalidomide. Thalidomide is a fusion of phthalimide (derivative of phthalic anhydride) and glutarimide (a derivative of glutamic acid) ring moieties.[1] Lenalidomide differs from its parent molecule in pthalimide ring, which is thought to be responsible for its more potent suppressive effect on tumor necrosis factor-α (TNF-α) production.[2]

The anti-inflammatory properties of thalidomide have led to its popularity in its use in erythema nodosum leprosum (ENL) where it is considered as the drug of choice. Lenalidomide due to its more potent anti-inflammatory action and less severe side effects can also be used for the above indication. It has a predictable tolerability profile and neurological side effects of thalidomide, including sedation and neuropathy, are lacking with this drug.[3],[4] Herein we report a case of ENL who developed adverse effects due to thalidomide and responded very well to lenalidomide without any recurrence over the last 1 year.


  Case Report Top


A 45-year-old man presented with complaints of multiple numb light colored patches over his back, trunk, and chest of 6 months duration. The patient also gave history of loss of sensation to touch, temperature, and pain in both hands and feet for the last 3 months. Dermatological examination revealed multiple, polysized, ill-defined hypopigmented patches tending toward symmetry extending over his back, trunk, and chest. There was Grade 1 thickening and Grade 1 tenderness in ulnar and common peroneal nerve of right side. Patient underwent slit skin smear which revealed a Bacteriological index of 3+. The patient was diagnosed clinically and bacteriologically as a case of Hansen’s disease (BL). He was started on 3 drug MDT. However, after 4 months of starting treatment he presented with sudden onset, multiple, red colored, raised, painful lesions over trunk and extremities of 3 days duration. The patient also had fever and myalgia for the past 2 days. The lesions erupted suddenly over lower limbs and gradually spread to involve upper limbs and trunk and were associated with a change of color from red to bluish red over the next 3 days.

Dermatological examination revealed multiple, discrete, round to oval, polysized erythematous, tender, firm, nodules present over bilateral upper extremities, lower extremities, and chest [Figure 1] and [Figure 2]. Hair, sweating, and sensations over the lesions were preserved. There was edema of the hands and feet.
Figure 1: Multiple, discrete, round to oval, polysized erythematous, tender, firm, nodules present over right shoulder and chest

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Figure 2: Few discrete, round to oval, polysized erythematous, tender, firm, nodules present near right antecubital fossa

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Skin biopsy from the nodule showed normal epidermis with clear grenz zone. Macrophage granulomas with occasional epithelioid cells and few lymphocytes were present in the dermis [Figure 3]. There was evidence of vasculitis in the form of damage to vessel wall, infiltration of vessel wall by inflammatory cell, and extravasation of RBCs. Subcutis showed the presence of lobular panniculitis [Figure 4].
Figure 3: Normal epidermis with clear grenz zone. Macrophage granulomas with occasional epithelioid cells and few lymphocytes present in the dermis. (H&E x 40)

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Figure 4: Presence of lobular panniculitis. (H&E x 40)

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The patient was diagnosed as a case of Hansen’s disease (BL) with Type II reaction. He was started on tab thalidomide 100 mg four times a day, whereas his MDT continued. His clofazimine was increased to 100 mg three times a day. However, after 2 weeks of treatment he started complaining of headache and excessive drowsiness during daytime which started hampering his daily routine. In view of the above complaints he was switched to tab lenalidomide 10 mg OD which he continued for 2 months. Later the dose was reduced to 10 mg alternate day for next 2 months post which it was stopped. The patient responded well to treatment with complete clearance of lesions 10 days after starting lenalidomide [Figure 5] and [Figure 6]. His neuritis reduced after 7 days of therapy. The headache and excessive drowsiness was not seen with lenalidomide. The patient is under regular follow-up with no recurrence of reaction 18 months post-stopping lenalidomide.
Figure 5: 10 days after lenalidomide: postinflammatory hyperpigmentation over both hands and chest

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Figure 6: 10 days after lenalidomide: postinflammatory hyperpigmentation near right antecubital fossa

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  Discussion Top


ENL is an immune complex-mediated reaction commonly seen with lepromatous pole of leprosy. Patients with high bacillary index (>4), intercurrent stress, infection, trauma, pregnancy, parturition, and surgical intervention are at increased risk for this reaction.

Earlier ENL was regarded as only immune complex-mediated reaction but now several other inflammatory mediators are considered in its pathogenesis.

Neutrophils are considered a histological hallmark of ENL. They are increased in number as well as associated with increased CD64 surface receptor, which is associated with activated neutrophils. This increase in neutrophil is mediated by TLR-2 activation which in turn activates interleukin (IL)-1 beta which subsequently along with interferon (IFN)-gamma increases E-selectin on endothelial cells. The above pathway is blocked by thalidomide and its congeners.[5]

TNF-alpha is also supposed to play a major role in the pathogenesis of ENL as is proved in multiple studies.[6] Lenalidomide causes a striking downregulation of TNF- α in which it is 50,000 more potent than its parent drug thalidomide. The inhibitory effect of thalidomide on TNF-α is a consequence of increased degradation of its mRNA due to the drug.[7],[8]

Apart from these lenalidomide also decreases other pro-inflammatory Th1 cytokines and vascular endothelial growth factor (VEGF) which also play a key role in pathogenesis of ENL [Figure 7].
Figure 7: Mechanism of action of lenalidomide

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Thalidomide even though the drug of choice is more commonly associated with somnolence, headache, peripheral neuropathy, thromboembolism, teratogenicity, and other adverse cutaneous drug reactions. Lenalidomide has lower incidence of adverse effects namely sedation, constipation, and neuropathy than thalidomide.[9]

Lenalidomide is used in the dosage of 25 mg for malignancies and lower dosage of 10 mg for myelodysplastic syndromes and maintenance dose for hematological malignancies. The drug is mainly excreted by the renal route with a half-life of 3 h and hence requires dose adjustment in renal disorders. In our patient, the drug was started at the lowest possible dosage of 10 mg to which he responded very well.[10]

ENL is also prone to recurrence with recurrent ENL being defined as repeated episodes of ENL occurring after 28 days of stopping treatment for ENL. Our patient has been under follow-up for the past one and half year with no evidence of recurrence.


  Conclusion Top


To the best of author’s knowledge, use of lenalidomide in ENL has not been reported so far in the literature. The case underscores the importance of use of lenalidomide in ENL which is a better and safer alternative to thalidomide. However, further well-designed controlled studies are required to investigate the drug’s efficacy and safety in ENL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.



 
  References Top

1.
Millrine D, Kishimoto T. A brighter side to thalidomide: Its potential use in immunological disorders. Trends Mol Med 2017;23:348-61.  Back to cited text no. 1
    
2.
Muller GW, Corral LG, Shire MG, Wang H, Moreira A, Kaplan G, et al. Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J Med Chem 1996;39:3238-40.  Back to cited text no. 2
    
3.
Zeldis JB, Knight R, Hussein M, Chopra R, Muller G. A review of the history, properties, and use of the immunomodulatory compound lenalidomide. Ann N Y Acad Sci 2011;1222:76-82.  Back to cited text no. 3
    
4.
Zagouri F, Terpos E, Kastritis E, Dimopoulos MA. An update on the use of lenalidomide for the treatment of multiple myeloma. Expert Opin Pharmacother 2015;16:1865-77.  Back to cited text no. 4
    
5.
Lee DJ, Li H, Ochoa MT, Tanaka M, Carbone RJ, Damoiseaux R, et al. Integrated pathways for neutrophil recruitment and inflammation in leprosy. J Infect Dis 2010;201:558-69.  Back to cited text no. 5
    
6.
Stefani MM, Guerra JG, Sousa AL, Costa MB, Oliveira ML, Martelli CT, et al. Potential plasma markers of type 1 and type 2 leprosy reactions: A preliminary report. BMC Infect Dis 2009;9:75.  Back to cited text no. 6
    
7.
Muller GW, Chen R, Huang SY, Corral LG, Wong LM, Patterson RT, et al. Amino-substituted thalidomide analogs: Potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 1999;9:1625-30.  Back to cited text no. 7
    
8.
Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993;177:1675-80.  Back to cited text no. 8
    
9.
Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36.  Back to cited text no. 9
    
10.
Chen N, Zhou S, Palmisano M. Clinical pharmacokinetics and pharmacodynamics of lenalidomide. Clin Pharmacokinet 2017;56:139-52.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]



 

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