Background

Similar to most chronic diseases in the current medical milieu, there is a constant interplay between therapeutics and pathophysiology. With the development of novel therapeutic agents with specific mechanisms of action and the knowledge of such mechanisms, new inroads have been made into our understanding of the pathophysiology of several diseases. This in turn has spawned further development of medical pharmacological therapies. The closer we get to understanding the molecular mechanisms of a disease, and in particular of HS, the greater our opportunity to pinpoint directed medical management. Nowhere does this ring more true

146 Sharon E. Jacob, Francisco A. Kerdel

Table 20.1. Biologic therapy in HS [5, 8-11]. (CD Crohn's disease, CR case report, CS case series, HS hidradenitis suppurativa, PC personal communication, UC ulcerative colitis)

Author Case Year Strength Age report of evi- (years)/

no. dence sex

Disease Bio- Outcome Outcomes dura- logic measures tion

(years)

Martinez

1

2001

CR

30/F,

6

Inflixi-

Resolution of

Remission

et al. [8]

HS + CD

mab

refractory nod-

6 months after

ules

two infusions,

maintained

with azathio-

prine

(adverse

reaction noted

after 2nd dose)

Katsanos

2

2002

CR

39/M

Unknown

Inflixi-

Remission

Remission

et al. [5]

HS + CD

mab

after 2 years

of infusions

Lebwohl and

3

2003

CR

21/M

2

Inflixi-

Complete re-

Disease

Sapadin [9]

HS +/- CD

mab

epithelializa-

resolution

tion

Adams

4

2003

CR

17/M

3

Inflixi-

Complete re-

Complete

et al. [10]

HS + UC

mab

mission

resolution

of pain,

tenderness,

purulence,

draining and

odor Induc-

tion of disease

remission

Adams et al.

5

2003

PC

Unknown

Unknown

Inflixi-

Remission

Successful

[10] (K.B.G.)

HS

mab

remission

Sullivan

6-10

2003

CS

51/F

20

Inflixi-

Patient report-

Patients'

et al. [11]

28/F

10

mab

ed disease

reported

36/F

20

activity scale

disease activity

57/F

44

Ability to

significantly

45/M

25

decrease

decreased

"standard"

within

All HS

systemic

3-7 days

medications

(p=0.0001)

(ciclosporin,

paired t test

prednisone)

Patients

reported de-

creased pain

after 24 h

Rosi et al.

11

2005

CR

30/F

1.5

Inflixi-

Improvement

No evidence

[12]

HS + CD

mab

of symptoms

of active in-

flammation

5 weeks into

therapy

than for the new biologic therapies. This is particularly important in HS, given that there is no universally effective medical therapy, and, furthermore, current medical management is marginally beneficial even when claimed to work.

While the etiology and pathogenesis of HS remain largely unknown, the disease has been shown to occur in association with other disorders of follicular occlusion, such as acne conglo-bata and dissecting cellulitis of the scalp. In these disorders, follicular occlusion leads to overgrowth of bacteria and subsequent neutrophilic inflammation. Many observations have been reported regarding the role of androgens/ hormones, obesity, and genetics, which may in addition influence the clinical picture [3, 4]. It is the reported association with Crohn's disease (CD), however, which has led to speculation and opportunities for novel management. It has been postulated that the two conditions share similar pathological immune mechanisms, such as increased levels of tumor necrosis factor alpha (TNFa) and neutrophilic chemotaxis [5]. This interesting co-occurrence of HS and CD highlights both the inflammatory nature of the disease and the rationale for using biologics known to be effective in CD [6].

There is evidence that infliximab is efficacious at stopping fistula drainage when used as a maintenance agent in fistulizing CD [7]. It is reasonable to suppose that if a patient sees inf-liximab-induced improvement of their CD fis-tulization, they would also see the healing of any co-existing HS with skin fistulization. A review of the literature demonstrates that this is indeed the case. The first three cases of effective treatment of HS with infliximab were in patients who had undergone the treatment for CD. At the time of writing this chapter, 11 cases of HS treated with infliximab have been reported in the literature. Of the 11 reported cases, 4 (36%) had been patients with associated CD (see Table 20.1) [5, 8-12]. Nevertheless, these preliminary cases demonstrate both the high de-

gree of efficacy of infliximab therapy for longstanding HS and that in some cases improvement was observed in as little as 3 days.

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