Abstract

This is a case report of a 41 year old multipara with human immunodeficiency virus (HIV) infection with an interesting history. She was initially commenced on a regimen of antiretroviral which included nevirapine in her non pregnant state. A change of drugs to replace nevirapine with efavirenz was instituted when skin rash was noticed. Unfortunately, she was recommenced on nevirapine when she became pregnant at 15 weeks gestation and developed symptoms of Stevens Johnson syndrome necessitating admission and treatment following which she made a full recovery. The presentation of this case highlights the importance of pharmacovigilance and health education to patients about adverse drug reactions.

Keywords: Nevirapine, Stevens Johnson Syndrome, Human immunodeficiency virus, pharmacovigilance.

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Introduction

Stevens Johnson syndrome is an immune complex mediated hypersensitivity complex that involves skin and mucous membranes (1). It is a serious systemic disorder with potential for severe morbidity and mortality (2), the mortality rate among patients is 23% at six weeks and 34% at one year (3). Aetiologic agents implicated in Stevens Johnson syndrome include drugs, infections, malignancy related and idiopathic (2, 4, 5).

There are increasing reports of Steven Johnson syndrome among HIV positive pregnant women with nevirapine being implicated in the aetiology (6, 7). We present a case report highlighting pitfalls in the prescription of nevirapine, the morbidity of this condition and the potential for the under-reporting of such occurrences.

Case history and examination

Mrs V.a.d. Was a 41 year old g 7 p 5 +1known HIV positive client with 5 living children. She had been diagnosed with HIV four years earlier, with a cd4 count of 69 cells per ml and commenced on haart. Initially, she was commenced on truvada (emtricitabine 200mg and tenofovir disopropyl fumarate 300mg) and nevirapine but later, nevirapine was replaced with efavirenz when she developed a mild skin rash with the use of nevirapine. She was also on daily co-trimoxazole and was doing well. She presented to the adult retroviral treatment clinic at 15 weeks gestation on the 7th of may 2013 with a one week history of itchy skin rash which initially started on the neck but progressed to form blisters, eventually rupturing leaving ulcers on the face, trunk, both upper and lower limbs and the vulva. The mucous membranes of the mouth and the conjunctiva were not spared as well. Her symptoms started three days after commencement of a new haart regimen comprising truvada and nevirapine when a urine pregnancy test confirmed pregnancy. See figures 1 and 2.

Figure 1. Mrs V.A.D with Oral and cutaneous lesions

Figure 2. Cutaneous lesions on her back

The initial symptom was mild and patient continued her medication in the hope that this will resolve spontaneously. With exacerbation of the symptoms, she represented to the ART clinic where a diagnosis of Stevens Johnson Syndrome was made, her medications were stopped and she was admitted to the ward for further care. Her vital signs on admission were a temperature of 37.2 degrees Celsius, respiratory rate of 18/minute, a pulse rate of 82/minute, Blood pressure of 110/70 mmhg. She was bed-ridden, with inability to eat due to the mouth ulcers and inability to defeacate.

Initial treatment consisted of investigations; a FBC which showed a total white cell count of 8,000 cells per ml and packed cell volume of 35%. The liver function tests and urea and electrolytes were all within normal range. Her CD 4 count was 350 cells /ml. Rehydration was commenced with intravenous fluid 55 dextrose saline one litre to be given eight hourly. Intravenous amoxicillin clavulanic acid 1.2g 12 hourly and metronidazole 500mg eight hourly, oral nystatin 100,000 iu six hourly and gentamycin eye drops were the medications given. Skin ulcers were treated with dermazin cream and intravenous hydrocortisone 100mg was given. A check on the pharmacy for the remnant of the nevirapine to obtain the batch number and expiry date for reporting was unrewarding as the drugs were said to have been destroyed by burning.

Over a period of three weeks on admission, her condition gradually improved. She began to tolerate oral feeds and ambulation became easier. The skin ulcers gradually healed. See figure 3.

Figure 3. Healed lesions on the leg

Her oral medications were recommenced as Truvada and efavirenz, haematincs were added and she was registered foe antenatal care in line with the principle of PMTCT (Prevention of mother to child transmission of HIV). An ultrasound scan done on admission confirmed a live singleton intrauterine gestation with a gestational age of 16 weeks and an expected date of delivery of 23/10/2013. Mrs V.A.D. was subsequently discharged and was seen at follow up a month later. She was cheerful, healthy looking but with residual hyperpigmented patches all over the body. Her CD 4 count was 365 cells /ml and she had started feeling foetal kicks. See figure 4 and 5.

Figure 4. Mrs V.A.D at first follow up

Figure 5. At second follow up

Discussion

The muco-cutaenous manifestations of Stevens Johnson Syndrome which include acute skin blisters and mucous membrane eruptions (8) were seen in this patient. These were severe enough to incapacitate the patient for about two weeks and are not unexpected (9). Before prescribing Antiretroviral drugs for patients, it is imperative to take a good history and educate the patient on adverse reactions associated with the drug and the need for prompt presentation to hospital should it occur (7, 10). This was not done in the case of this patient. The management principle which involves recognition and prompt withdrawal of causative agents, fluid therapy, skin care, antibiotics and steroid use were adhered to. These contributed in no small measure to the recovery of this patient. It is imperative to mention here that in addition, co-management with other specialists including the dermatologist, ophthalmologist, respiratory physician, plastic surgeon and gastroenterologist will also help in severe cases (11). Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problem (12). This helps to prevent further damage and prevent future occurrence. Various studies have shown that pharmacovigilance awareness is low and practice still needs to be improved in our environment (13, 14). The destruction of the drugs in the pharmacy is proof that a lot needs to be done in this area. Morbidity and mortality from Stevens Johnson Syndrome in pregnant women with HIV can be further reduced if basic principles of good history taking, counseling, high index of suspicion for early detection of reactions, aggressive management and proper documentation and notification of cases are carried out.

References

  1. French L.E. Toxic Epidermal Necrolysis and Stevens Johnson Syndrome: Our Current Understanding. Allergol Int. March 2006 : 55 (1) : 9-16
  2. Stephen C. Foster, Rola Ba-Abbad, Erik Letko, Steven J Parillo. Stevens Johnson Syndrome. Emedicine. Https://emedicine.medscape.com/article/1197450-overview#a1. Jan 17 2019.
  3. Sekula P, Dunant A, Mackenhaupt M, Naldi L, Bouwes Bawink JN, Halery S, Kardaun S, Sidoroff A, Liss Y, Schumacher M, Roujeau JC. Comprehensive Survival Analysis of A Cohort of Patients with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis. J Invest. Dermatol. 2013; 133 (5): 197-204
  4. Sendi P, Graber P, Lepere F, Schiller P, Zimmerli W. Mycoplasma Pneumoniae Infection Complicated by Severe Mucocutaneous Lesions. Lancet Infec Dis. April 2008. 8(4): 268
  5. Kumar P.N.S, Thomas B, Kumar K, Kumar S. Stevens-Johnson Syndrome- Toxic Epidermal Necrolysis (SJS-TEN) Overlap Associated with Carbamazepine Use. Indian J Psychiatry. 2005; 47(2): 121-123
  6. Sulayman H, Wanoyi I, Ramadan A, Aliyu Z, Bush M. Steven-Johnson Syndrome seen in A HIV Positive Pregnant Patient: A Case Report. Poster Presentations/ International Journal of Gynecology and Obstetrics 107S2 (2009). P506: S557
  7. Dube N, Adewusi E, Sunnmer R. Risk of Nevirapine – Associated Stevens Johnson Syndrome Among HIV Infected Pregnant Women: The Medunsa National Pharmacovigilance Centre, 2007-2012. SAMJ Vol 103 No. 5 May 2013 : 322-325
  8. Chen K.T, Twu S.J, Chang H.J, Lin R.S. Outbreak of Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis Associated with Mebendazole and Metronidazole Among Filipino Labourers in Taiwan. Am J. Public Health. 2003; 93(3): 489-492
  9. Agbogoroma C.O, Uwaezuoke T, Jibrin P.G. Stevens Johnson Syndrome Associated with Nevirapine Use in an HIV-Positive Pregnant Woman: A Case Report. West Afri J Med. 2010. May-Jun: 29 (3) : 187-9
  10. Catherine Orreli. Antiretroviral Adverse Drug Reaction and Their Management. CME June 2011. Vol. 29 No. 6: 234-237 www.cmej.org.za
  11. Falodun O, Ogunbiyi A. Dermatological Emergencies: Current Trends in Management. Annals of Ibadan Postgraduate Medicine. Vol 4. No. 2. Dec 2006 : 16-21
  12. WHO/Pharmacovigilance. Www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/
  13. Showande JS, Oyelola FT. (2013).The Concept of Adverse Drug Reaction Reporting: Awareness among Pharmacy Students in A Nigerian University. Internet Journal of Medical Update. 8 (1): 24-30
  14. Ohaju-Obodo J. O, Iribhogbe O. I. Extent of Pharmacovigilance among Resident Doctors in Edo and Lagos State of Nigeria. Pharmacoepidemiol Drug Saf. 2009; 19 (2): 191-5