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Interesting rare case of polyarteritis nodosa related to hepatitis B virus and plasma exchange role? – A case report and review of the literature


1 Department of Transfusion Medicine and Hematology, TMC, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka; Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India

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Date of Submission08-Jun-2022
Date of Acceptance17-Jul-2021
Date of Web Publication26-Sep-2022
 

   Abstract 

Immune-mediated diseases wherein immune complex-mediated injury is predominant; plasma exchange remains a therapeutic option for vasculitis. Hepatitis B virus-associated polyarteritis nodosa (HBV-PAN) wherein immunosuppressants can be contraindicated, plasma exchanges have a proven role when combined with antiviral therapy. Plasma exchange by hastening the clearance of immune complexes is beneficial in acute organ dysfunction. A 25-year-old male presented with complaints of generalized weakness, tingling numbness and weakness of extremities, joint pain, weight loss, and rashes over arms and legs for 2 months. Hepatitis B workup showed high viral loads of HBV (34 million IU/ml) and hepatitis e antigen positivity (1129.06 U/ml). Cardiac workup showed elevated cardiac enzymes and decreased ejection fraction (40%–45%). The finding of contrast-enhanced computed tomography (CECT) chest and abdomen with CT angiogram abdomen was steady with medium vessel vasculitis. A diagnosis of vasculitis with probable etiology of HBV-related PAN with mononeuritis multiplex and myocarditis was made. He was treated with steroids, tablet tenofovir, and 12 sessions of plasma exchanges. On average, 2078 ml of plasma was exchanged during each session with 4% albumin as a replacement fluid using central femoral line dialysis catheter as vascular access on automated cell separator Optia ®Spectra (Terumo BCT, Lakewood, Co). He was discharged with the resolution of symptoms, including myocarditis and increase in power strength and still in follow-up. The present index case indicates that antiviral combined with plasma exchange after short-term corticosteroids is an effective therapy for HBV-PAN. TPE can be used as adjuvant therapy along with antiviral therapy in a rare disease like HBV-related PAN.

Keywords: Hepatitis B virus-associated polyarteritis nodosa, the American Society for Apheresis, therapeutic plasma exchange


How to cite this URL:
Tripathi PP, Sharma RR, Kopp CR, Basnet A, Ramakrishnan S, Lamba DS, Hans R, Sharma A. Interesting rare case of polyarteritis nodosa related to hepatitis B virus and plasma exchange role? – A case report and review of the literature. Asian J Transfus Sci [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajts.org/preprintarticle.asp?id=356896



   Introduction Top


A well-known systemic necrotizing vasculitis form known as polyarteritis nodosa (PAN) affects predominately the medium-sized arteries.[1] Although the first case of PAN was reported in 1861 by Kussmaul and Maier, hepatitis B virus (HBV)-PAN was described much later in the 1970s.[2],[3] The annual incidence of PAN in the general population was reported from 4.6 to 77/1,000,000 in the frequency of low-to-high hyperendemic population (Alaskan population).[2] Pathogenesis of HBV-PAN is likely due to the deposition of immune complexes in vessel walls resulting in vascular injury.[4] A rare complication of chronic hepatitis B infection, PAN occurs only in up to 5% of chronic HBV patients.[2] Due to vaccination against hepatitis B and pretransfusion blood products screening for HBsAg, the incidence of HBV-related PAN is in decreasing trend.[4] Conventional therapy of corticosteroids and adjuvant therapy of cyclophosphamide is being still used in HBV-PAN to control the infection status; however, it may lead to an increase in viral load causing fulminant liver failure.[5] Inpatient, where therapeutic plasma exchange (TPE) was done along with antiviral drugs, had shown good response.[6] According to the American Society for Apheresis (ASFA) 2019, HBV-PAN comes under category II (2C) and TPE had a supportive role in the therapeutic efficacy.[7] The aim of this study is to review 35 years of literature (1985–2020), including case reports and clinical trials, determine early initiation and increased numbers of plasma exchanges in HBV-related PAN, and discuss its role in patient improvement. Here, we report a case of PAN that was associated with hepatitis B which improved with TPE therapy.


   Case Report Top


A 25-year-old man presented with complaints of generalized weakness, tingling numbness with weakness of extremities, joint pain, weight loss, and rashes over arms and legs for 2 months. History began with pain over both the calves during walking associated with tightness over calf muscle requiring rest after strolling every 100 m. Advance, it was related to shortness of breath on strolling for another 20 days term. It was not related to cough, orthopnea, paroxysmal nocturnal dyspnea, or palpitations. The patient moreover complained of numbness of left upper limbs 45 days ago taken after by right upper limbs 40 days ago, beginning over 5th finger and advancing to include other fingers and medial aspect of palm and distal lower arm coming about in wrist drop as appeared in [Figure 1]. In arrangement to the upper limbs, he too complained of numbness over both lower limbs, 40 days ago (right leg followed by left leg) at the first beginning over the sole of the foot, spreading to the dorsum of the foot-related with weakness of both feet and failure to bear weight on both lower limbs. It was not related to any slippage of shoes or loss of sensation of warm and cold. There was a history of pain in small joints of both hands and maculopapular rashes with depigmentation over respective upper and lower limbs related to tingling. He moreover complained of testicular pain on and off, pain within the guts postprandial, and a history of weight loss. He had a history of two generalized tonic–clonic seizures, conceded to a neighborhood exterior health center for the abovementioned indications, and began steroid-based treatment. As there was no response to steroids, he alluded to our tertiary care center for further management. Significant history of Male sex with Male was present. On examination, the patient was hypertensive, and skin injuries over both upper and lower limbs and depigmented ulcerative macular regions were displayed as appeared in [Figure 2].
Figure 1: Wrist drop

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Figure 2: Cutaneous ulcer in the right lower limb

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On examinations, power and reflexes in both upper limbs (at shoulder and elbow joints 4/5, wrist joints 1/5) and lower limbs (at hip and knee joints 4/5, lower leg joints 1/5), and reflexes (supinator, biceps, triceps, knee 3+, lower leg-missing and Plantar–Mute) were diminished separately. All scheduled examinations counting total blood count, liver function test, and renal function tests, were inside typical extent. Hepatitis B workup appeared with high viral loads of HBV ([patient's HBV-34 million IU/ml] [normal range-10-1,000,000,000 IU/mL]) and hepatitis e antigen positivity. Cardiac workup appeared raised cardiac enzymes (patient's creatine phosphokinase-MB, troponin T, and troponin I are 374 U/L, 32 ng/dl, and 45 ng/dl, respectively, and the normal range is >161 U/L, 0.01–25 n/dl and 0.04–40 ng/dl, respectively) and two-dimensional echo appeared ejection fraction of 40%–45%. The nerve conduction study was suggestive of sensorimotor axonal polyneuropathy. The finding of CECT chest and abdomen with CT angiogram abdomen was steady with medium vessel vasculitis [Figure 3] and [Figure 4]. Sural nerve biopsy showed fibrinoid necrosis and inflammation within the vasa nervorum. On the premise of history, examinations, and investigations, a diagnosis of vasculitis with likely etiology of HBV-related PAN with the affiliation of mononeuritis multiplex and myocarditis was made. Treatment counting steroids (1 mg/kg for 1 month) in conjunction with tablet tenofovir (200 mg/day) was begun and a call for helpful TPE was started. After a starting appraisal, plasma exchange for this patient was begun on each alternate day. The estimated total blood volume of the patient was 2925 ml with a weight of 45 kg and the mean plasma volume was 1783.33 ml. Add up to 12 procedures of plasma exchange were performed utilizing Optia ®Spectra (Terumo BCT, Lakewood, CO) cell separator. On average, 2080.6 ml of plasma was exchanged using 5% human serum albumin and 0.9% normal saline as replacement fluid (80: 20) using both peripheral vein and central venous line catheters as access. Calcium gluconate (1%) infusion was given in all procedures through the separate venous line and in replacement fluids also. The patient was monitored for any signs of adverse effects. The patient had hypotension during one procedure which was managed conservatively with intravenous fluid bolus (0.9% normal saline).
Figure 3: CT angiogram showing multiple intraparenchymal renal artery aneurysms. CT: Computed tomography

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Figure 4: CT angiogram showing a beaded appearance of hepatic arteries. CT: Computed tomography

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Effectiveness of therapeutic plasma exchange with follows up

The patient showed signs of improvement with each plasma exchange procedure in terms of an increase in muscle power [Table 1]. At the time of discharge, the patient had significant improvement in terms of mobility; he was able to sit up from a bedridden state. He was able to eat himself and his appetite increased. Pain and tingling sensation over both lower limbs decreased. Skin lesions were healed over bilateral lower and upper limbs and resolution of symptoms including myocarditis. The sensory loss disappeared and the wrist along with foot drop diminished. The patient was discharged in stable condition after 1 month of hospital stay.
Table 1: Relationship between plasma exchange procedure and power changes

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Follow-up: At 2 months of follow-up after his discharge, the patient recovered and was able to do his routine activities. Although foot drop still persisted, he was advised to wear crippling shoes and able to stand with support. Two months later, Hepatitis B (e) antigen and Hepatitis B surface antigen (HBeAg and HBsAg) could no longer be detected and lamivudine was stopped. After 5 months of follow-up, he was able to do routine activities including walking without support. He gained weight and was socially active. On further follow-up at 1 year, the patient was active and working normally.

Review of literature

We also conducted a literature review of the PubMed database (from 1985 up to December 31, 2020) to identify the cases or case series describing TPE as a treatment modality in cases of HBV-related PAN. The following search term was used in different combinations: (“hepatitis B-related PAN and plasma exchange role” or “beneficial role of plasma exchange and plasmapheresis in HBV-related PAN”). Only eight results were found in the literature while using plasma exchange and hepatitis B-related PAN as a keyword out of 23 results. If hepatitis B-related PAN as a keyword was used, 12 results were found. Again using HBV-related PAN and treatment as keywords, 10 results were found. As per our topic, plasma exchange and its role in HBV-related PAN, only eight studies were relevant. Most of the studies were from 1991–1996. This showed the prevalence of this disease as a rare identity. The relevant full texts, abstracts, and cross-references were then obtained and reviewed in detail. Short details of the literature review are shown in [Table 2], where the beneficial role of plasma exchange was estimated.
Table 2: Short summary of review of literature

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   Discussion Top


Within the Indian subcontinent, HBV has customarily considered an uncommon illness with a predominance rate of around 3%.[15],[16] However, it were a couple of cases of HBV-related PAN have been detailed with no legitimate treatment convention. However, only a few cases of HBV-related PAN have been reported with no proper treatment protocol. Corticosteroids and immunosuppressive drugs and role in HBV-related PAN are already established to reduce anti-inflammatory organ damage and HBeAg seroconversion.[11] Long-term viability for steroid utilization is still not demonstrated in writing. The expansion of antiviral therapy was a modern approach separated from steroids counting interferon-alpha, tenofovir, and lamivudine. Antiviral treatment targets the change of dynamic inveterate hepatitis B to the inert hepatitis B carrier state in HBV-related containers and diminishment of the generation of HBV antigens.[11] A strong correlation is already established between baseline ALT level and HBeAg seroconversion rate under antiviral agents.[17] Steroids enhanced the priming of virological response to antiviral agents resulting in ALT rebound.[18] Concurrent use of steroids with antiviral drugs comes about in quicker infection control in HBV-related containers. It is recommendable to utilize antiviral treatment until HBeAg seroconversion happens. TPE besides steroids did not appear any advantageous part in cases of PAN without HBV contamination in terms of introductory infection control or survival, even in severe PAN. The immune complex composed hepatitis B antigen and antihepatitis antibodies has been seen in the vascular lesions in HBV-related PAN. More amount of immune complex as inactive vascular lesions and lesser amount of these complexes in healed lesion form the basis of pathogenicity in HBV-related PAN.[16] This pathogenesis forms the basis of a treatment to clear the immune complex. TPE helped the index case by removing immune complexes, which were major contributors to vessel inflammation and an antiviral agent was added to facilitate immune-complex clearance by diminishing the virus load and, eventually, to stop viral replication. In truth, TPE without the expansion of corticosteroids or cyclophosphamide can control the course of HBV-related PAN.[19] This is so far the first case reported to our knowledge which gets extremely benefitted by TPE in a developing country. Another way round, TPE has a limited role including recovery from few symptoms and limits the intensity of squeal; however, more studies are required to prove its role in HBV-related PAN.[14] The role of plasma exchange therapy has been widely used over the past few decades, and prospective new trial regimens have further solidly customized their indication and reduced PE numbers. Regardless of that, TPE has still a role as an adjuvant to other treatments. Intravenous immunoglobulins and other immunomodulating therapy have started the outstripping of plasma exchange, but indications of TPE are not strictly superimposable, especially in such a case of HBV-related PAN.[20] At present knowledge, no fixed protocol is there for these kinds of patients, and further studies are now necessary to determine their efficacy. Moreover, TPE removes the fractionation of antibodies from the circulation with each session and causes immunomodulation, immunoregulation, and removal of inflammatory mediators, which are the adjuvant benefits of TPE.[21]


   Conclusion Top


According to the latest guidelines of ASFA, recommended HBV-PAN comes under category II (2C), and TPE had a supportive role in the therapeutic efficacy. Similarly, our case report highlights the role of TPE as effective adjuvant therapy in HBV–PAN to antiviral and short-term corticosteroids. The rarity of this case in recent times emphasized developing a protocol for such rare cases to achieve clinical recovery.

Declaration of patient consent

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

Acknowledgments

Parmatma Prasad Tripathi, Sharanya Ramakrishnan, and Amal Basnet were involved in patient management and the initial drafting of the manuscript.

Chirag R Kopp was involved in patient management and review of the manuscript.

Divjot Singh Lamba was involved in patient management and review of the manuscript.

Rekha Hans was involved in patient management and review of the manuscript.

Aman Sharma was involved in patient management and the final review of the manuscript.

Ratti Ram Sharma was involved in patient management, final drafting, and final preparation of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Lightfoot RW Jr., Michel BA, Bloch DA, Hunder GG, Zvaifler NJ, McShane DJ, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990;33:1088-93.  Back to cited text no. 3
    
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Hess G, Manns M, Hütteroth TH, Meyer zum Büschenfelde KH. Discontinuation of immunosuppressive therapy in hepatitis B surface antigen-positive chronic hepatitis: Effect on viral replication and on liver cell damage. Digestion 1987;36:47-54.  Back to cited text no. 5
    
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Guillevin L, Lhote F, Sauvaget F, Deblois P, Rossi F, Levallois D, et al. Treatment of polyarteritis nodosa related to hepatitis B virus with interferon-alpha and plasma exchanges. Ann Rheum Dis 1994;53:334-7.  Back to cited text no. 6
    
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Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, et al. Guidelines on the use of therapeutic apheresis in clinical practice – Evidence-based approach from the writing committee of the American Society for Apheresis: The eighth special issue. J Clin Apher 2019;34:171-354.  Back to cited text no. 7
    
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Guillevin L, Lhote F, Leon A, Fauvelle F, Vivitski L, Trepo C. Treatment of polyarteritis nodosa related to hepatitis B virus with short term steroid therapy associated with antiviral agents and plasma exchanges. A prospective trial in 33 patients. J Rheumatol 1993;20:289-98.  Back to cited text no. 10
    
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Deeren DH, De Backer AI, Malbrain ML, Verbraeken H, Blockmans D. Treatment of hepatitis B virus-related polyarteritis nodosa: Two case reports and a review of the literature. Clin Rheumatol 2004;23:172-6.  Back to cited text no. 11
    
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Takeshita S, Nakamura H, Kawakami A, Fukushima T, Gotoh T, Ichikawa T, et al. Hepatitis B-related polyarteritis nodosa presenting necrotizing vasculitis in the hepatobiliary system successfully treated with lamivudine, plasmapheresis and glucocorticoid. Intern Med 2006;45:145-9.  Back to cited text no. 12
    
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Deléaval P, Stadler P, Descombes E, Hecker E, Schrago G, Chizzolini C, et al. Life-threatening complications of hepatitis B virus-related polyarteritis nodosa developing despite interferon-alpha2b therapy: Successful treatment with a combination of interferon, lamivudine, plasma exchanges and steroids. Clin Rheumatol 2001;20:290-2.  Back to cited text no. 13
    
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Guillevin L, Mahr A, Cohen P, Larroche C, Queyrel V, Loustaud-Ratti V, et al. Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa. Arthritis Rheum 2004;51:482-7.  Back to cited text no. 14
    
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17.
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18.
Lhote F, Guillevin L. Indications for plasma exchange in the treatment of polyarteritis nodosa, Churg-Strauss syndrome and other systemic vasculitides. Trans Sci 1996;17:211-23.  Back to cited text no. 18
    
19.
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20.
Guillevin L, Pagnoux C. Indications of plasma exchanges for systemic vasculitides. Ther Apher Dial 2003;7:155-60.  Back to cited text no. 20
    
21.
Tripathi PP, Sharma RR, Chhabria B, Hans R, Sehgal IS. Therapeutic plasma exchange: A lifesaving therapy in case of ANCA-associated vasculitis with diffuse alveolar hemorrhage. Indian J Crit Care Med 2021;25:828-9.  Back to cited text no. 21
    

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Correspondence Address:
Ratti Ram Sharma,
Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.ajts_70_22



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