ABSTRACT diagnosis of DHS and to develop screening policies

ABSTRACT

Dapsone is a sulfone derived drug used
in the treatment of leprosy and several chronic inflammatory dermatological
diseases. Dapsone therapy rarely develop Dapsone hypersensitivity syndrome (DHS)
characterized by fever, hepatitis,generalized exfoliative dermatitis and
lymphadenopathy and is potentially fatal. We present a case report of a middle
aged female patient with a recent history of antecedent dapsone exposure of 100
mg daily for 2 weeks. She developed fever after 10 days of exposure to dapsone
therapy and was treated in various primary and tertiary centers for features of
sepsis. When presented to us, she  had
clinical features of multi-organ dysfunction and intractable sepsis. She was
successfully managed with intravenous corticosteroids and other supportive
therapy.This case of DHS is unique due to pulmonary, hepatic, colonic involvement
along with secondary bacterial and fungal infection, which  raises the risk of mortality. As Dapsone is a
mainstay in the treatment several infections and inflammatory conditions, more
research has to be done to characterize markers for diagnosis of DHS and to
develop screening policies prior to initiation of Dapsone therapay.

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Key words: Dapsone, Dapsone hypersensitivity,Exfoliative
dermatitis.

INTRODUCTION

Dapsone belongs to the sulfonamide drug
class. It was initially used to treat leprosy and later it was also found to
have anti-inflammatory properties. At present, it is used in a wide variety of dermatological
conditions, especially those with a neutrophil predominance as dapsone inhibits
neutrophil activation and recruitment through a number of pathways. The
effective dose of Dapsone is 100 mg daily, and a maximum up to 300 mg daily can
be used 1. Generally Dapsone is well tolerated,but at an incidence of 0.2-
0.5 %, it can cause DHS,which  is a form
of drug induced hypersensitivity syndrome, also known as DRESS       (Drug, rash, Eosinophilia and systemic
symptoms) 2. It also typically occurs as a reaction to drugs like
Carbamazepine, Phenytoin, Phenobarbital, Allopurinol, Sulfasalazine and Minocycline,
which mimics a severe form of sepsis. DHS is characterized by fever, rash and
multi- organ failure. It can be fatal and cause irreversible organ damage. The
mortality associated with DHS is 12-23%. Generally DHS can develop in 1-8 weeks
after Dapsone initiation. But in some cases, it can occur in as long as six
months after treatment initiation or in as short as 6 hours in previously
sensitized patients 3.

 

 

 

 

 

CASE
REPORT

A 52 years old  Indian female presented with fever of twenty
days duration associated with itching all over her body.She  had complaints of breathing difficulty of ten
days duration not associated with cough. She also complained of abdominal pain
associated with loose stools of ten days duration. Her medical and medication history
revealed that two months prior to current admission, she was treated with tablet
dapsone100 mg daily by a dermatologist for suspected dermatitis. She developed
fever and other constitutional symptoms after 10 days of exposure to Dapsone,
following which Dapsone was withdrawn on the 14th day. This was
followed by admission at a local hospital 
and even in a tertiary care center, wherein her symptoms worsened. Thorough
examination of  her previous medical
reports revealed that she was diagnosed to have hepatitis and a chest infection
for which she was treated with high-end antibiotics and bronchodilators.

On 
physical examination, she was pale,afebrile and had Icterus. She was
found to have  continuous hyperpigmented exfoliative
skin lesions all over her body, including face.Electro cardiography showed
sinus tachycardia. Ultra sonography of abdomen showed mild hepatomegaly with moderate
fatty infiltration, splenomegaly, right minimal pleural effusion with
consolidation, and also edematous bowel wall thickening of the ascending colon.
Colonoscopy revealed no abnormalities. Blood culture was sterile initially.
Sputum culture showed moderate growth of budding yeast.Stool and urine culture
was negative.Evaluations for her infectious etiologies were negative, this
included hepatitis panel, Human Immuno Virus, Hepatitis B surface Antigen, Anti
Leptospira IgM Antibody, Weilfelix test and Scrub typhus IgM Antibody.

Laboratory investigations showed anemia,
eosinophilic leucocytosis, deranged liver enzymes, hypoalbuminemia along with raised
lactate dehydrogenase and procalcitonin level  
(Table 1, 2).  A diagnosis of DHS with
co-existing secondary sepsis was made, based on the patient’s treatment
history, exfoliative dermatitis and multiorgan dysfunction with reasonable time
relationship to Dapsone exposure.

During the hospital stay, our  patient had high grade fever,dyspnea with
wheezing and loose stools. From second day she experienced, productive cough, and
her peripheral capillary oxygen saturation had dropped below 85%. Systemic
hydrocortisone 50 mg every 8 hours was started from the second day. Bronchodilators,
antihistamine, antibiotics and antifungal along with supportive therapy was
provided.Least possible medications were prescribed to prevent further drug
induced problems. She was also monitored for Dapsone induced secondary seizure.

The erosions on skin started healing
dramatically after 2 days of corticosteroid therapy and no acute symptoms were
noted.  On eighth day 1 unit of packed
cell transfusion was done. She was discharged on day 9 with oral
corticosteroids, antihistamine and other supportive medications.

 

Table
1 : Abnormal parameters in complete blood count

Laboratory
Parameters

Day 1

Day 4

Day 7
 
 
 

RBC (×106/µL)
Ref :
(4 – 4.8)

2.43

2.05

1.95

Haemoglobin
(g/dl)
Ref:
(12-15)

8.5

7.1

6.6

PCV  (%)
Ref:
(36-46)
 

25

21.5

20.4

MCV
(fL)
Ref:
(80-100)

102.9

104.9

104.5

MCHC
(g/dl)
Ref: (32-35)

34

33.3

17

RDW
(%)
Ref :
(10-15)

16.7

18.3

17

WBC ((×103/µL)
Ref:
(4-10)

19.6

10.1

9

Monocyte(%)
Ref:
(20-40)

15.1

4.1

6.1

Eosoninophil
(%)
Ref:
(1-6)
 

16.3

19.7

0

Absolute
eosinophil (×103/µL)
Ref:
(0.02-0.5)

2

3.2

0

ESR(mm)
Ref:
(4-12)
 

 

17

38

Lactate
dehydrogenase(U/L)
Ref:
(135-214)
 

1149

 

 

Procalcitonin
(g/ml)
Ref :