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194
K. Zarchi et al.
Secondary lesions include cutaneous ulcerations, pyogenic granulomas, and hypertrophic
scars, with the latter appearing as indurated
plaques or linearly ropelike scars. In contrast to
closed comedones, which never occur in
HS-affected areas, multiple, big, open comedones
(the so-called tombstone comedones) may be
seen in previously active areas.
Biopsies are rarely needed as the diagnosis is
based on the clinical presentation; nonetheless, in
some cases, differentiation from other skin diseases, such as pyoderma gangrenosum and cutaneous Crohn’s disease, might be difcult and
require histopathological investigations. The
characteristic histological ndings include follicular hyperplasia and hyperkeratosis, local
inltration of inammatory cells, formation of
sinus tracts, and presence of necrosis.
Microbiological examinations most frequently
fail to identify pathogens [2].
Fig. 27.1 Hurley stage II characterized by recurrent nodules and abscesses, formation of sinus tracts, and scarring.
At this stage, zone with normal skin remains
Fig. 27.2 Hurley stage III characterized by diffuse
involvement of the area with multiple interconnected
sinus tracts
tiple interconnected sinus tracts (Fig.27.2) [4]. The
majority of patients suffer from mild disease corresponding to stages I and II, while a smaller proportion progresses to severe disease which usually
predominates in hospital populations.
27.3 Pathophysiology
The folliculo-pilosebaceous unit is the primary
focus of the pathologic processes involved in
hidradenitis suppurativa. The etiology of HS is
multifactorial, encompassing genetic and environmental factors, lifestyle, hormonal status, and
microbiota. These factors lead to immune activation around the terminal hair follicles and hyperkeratosis (thickening of the horny layer) in the
infundibulum. Different theories have been proposed to explain the pathogenesis. These include
the suggestion of an immune response dysfunction, as it has been proposed that the disease is a
result of an inappropriate immunologic response
to the normal skin ora, similar to the pathogenic
processes involved in Crohn’s disease. Indeed,
elevated levels of proinammatory cytokines,
including tumor necrosis factor-α and
interleukin-1β, and involvement of the interleukin- 12–interleukin-23 pathway have been shown
[2, 5].
Further, the lack of expression of human betadefensin- 2, an important antimicrobial peptide of
the innate immune system against Gram-negative
bacteria, in HS lesions supports this theory.
27 Hidradenitis Suppurativa
195
However, the histopathological ndings in early
disease and investigations of basal membrane
zone in the folliculo-pilosebaceous unit point
towards a structural defect in the sebofollicular
junction as the possible main cause [6]. It is
hypothesized that mechanical trauma makes the
structurally defective folliculo-pilosebaceous
unit release keratin and other mediators, thereby
triggering inammation and inducing tissue
destruction and necrosis.
The possibility of HS being a defect in wound
healing has also been discussed. It has been
hypothesized that whereas breaches of the follicular epithelium are common following infections
or physical trauma, the perpetuation of the subsequent inammatory process which could lead to
HS is not. It may, therefore, be speculated that a
disturbed wound-healing process following the
inammatory stage occurs as a major factor in
HS.This theory is supported by the detection of
highly elevated levels of matrix metalloproteinase- 2 in keratinocytes, broblasts, sweat glands,
and hair follicles in lesional HS skin, indicating
dysregulated tissue repair and reconstruction following unspecic tissue damage [7].
27.4 Treatment
Treatment of hidradenitis suppurativa is often a
challenge [8]. By the time the diagnosis is made,
most patients have been treated with short-term
antibiotic regimens for several years without
experiencing any effect, as the lesions are commonly misinterpreted as furunculosis or common
abscesses. Establishing a strong alliance with the
patient, attempting to restore the patient’s faith in
the doctor-patient relationship, and explaining
the uctuating nature of the disease are highly
benecial in minimizing the risk of low patient
compliance. This is especially important in the
case of resistant disease, where several therapeutic approaches might be carried out until the one
or the combination inducing sufcient improvement is found.
Mild disease is often managed with topical
therapy, such as topical clindamycin, or occasional intralesional glucocorticoid injections.
However, in case of moderate to severe disease,
topical agents are inadequate and systemic therapy is usually indicated. Systemic treatment
options include oral antibiotics with immunomodulatory properties such as tetracycline, doxycycline, clindamycin, and rifampicin;
antiandrogenic therapies; and systemic immunosuppressive therapy, including tumor necrosis
factor-α inhibitors [1, 2]. Adalimumab was the
rst FDA- and EMA-licensed biologic agent for
the management of moderate to severe
HS. Immunomodulation targeting IL-1, IL-12/
Th1, and IL-23/Th17 pathways is rapidly becoming the cornerstone of therapy for moderate to
severe HS.
In elements refractory to medical treatment
and in the presence of scarred lesions, surgery,
nonetheless, is a mainstay of therapy. Surgical
approaches include exteriorization (“deroong”
of sinus tract, abscesses, and cysts [Fig. 27.3])
and surgical excision of lesional skin, with radical excisions being associated with lower recurrence rates. Alternatively, destruction of lesional
hair-bearing skin is achieved using ablative CO2
laser [9]. The surgical and ablative laser
approaches are based on the removal/destruction
of the cutaneous structures involved in the disease, thereby causing open wounds requiring closure or management.
Primary suture, skin graft, or ap reconstruction can be used to close the wounds depending
on the extent of procedure, or closure may be
achieved by secondary intention. Generally, sec-
Fig. 27.3 “Deroong” of a sinus tract
196
K. Zarchi et al.
ondary intention healing is recommended for all
but the smallest excisions. A comparison of skin
grafting versus closure by secondary intention
using foam dressing in patients undergoing bilateral excision revealed that skin grafting led to
more rapid healing; however, closure by secondary intention provided good cosmetic results and
avoided the need for immobilization and a painful donor side and was preferred by the patients
[10]. Long-term evaluation of healing by
secondary intention suggests acceptable to excellent outcome qualities.
Secondary healing requires suitable bandaging for periods of up to 12weeks. Since the disease affects concave surfaces of the body, it
presents a practical challenge. Appropriate nonadherent dressings, such as foams, siliconecoated dressings, alginates, and hydrocolloids,
are generally better suited to convex surfaces.
Bandage type may be adjusted during the healing
process as per normal practice; for example, the
initial combination of a saline gel and a silicone
dressing may be gradually replaced by silicone
dressing and ultimately a simple bandage to protect the nal epithelialization of the wound.
Individual adjustments may need to be performed, and once the wound is fully covered by
granulation tissue, some patients prefer to avoid
bandages all together. This non-recommended
patient behavior most likely reects the patients’
experience with chronic suppurating preoperative lesions.
Vacuum-assisted closure (VAC) may be used
to promote angiogenesis of the underlying subcutaneous tissue, reduce bacterial counts, and stabilize skin grafts. VAC has been successfully used
in the treatment of large postoperative wounds.
lems to the patients such as pain, tenderness,
visible scars, suppuration, and malodor; hence,
therapeutic decisions should address all those
issues. Effective bandaging represents one of
the challenges. Bandages should provide a
secure and comfortable barrier against malodorous leakage and be absorbent to prevent maceration of the skin, easy to use, and inexpensive
[11, 12]. Currently, no bandage meets all these
requirements, and the available solutions are,
therefore, combinations of products that are
both expensive and difcult to apply to inverse
area. As a consequence, patients are often forced
to turn towards alternative and inexpensive solutions such as sanitary pads, which are not
designed for this purpose (Fig.27.4). The morbidity due to HS is such that this issue of adjuvant therapy warrants more attention by
healthcare providers than it currently receives. It
is strongly recommended to address the practical problems of this hitherto neglected group of
patients by providing appropriate attention to
improved adjuvant therapy.
27.5 Adjuvant Therapy
Although the primary aim of therapy remains
the elimination or a substantial reduction in the
inammatory activities and the excision of
severely involved lesional skin, providing adjuvant therapy throughout the disease course is
necessary to improve the patients’ quality of
life. The disease presents many practical prob-
Fig. 27.4 Many HS patients are forced to use sanitary
pads due to the lack of inexpensive appropriate dressings
27 Hidradenitis Suppurativa
197
27.6 Conclusion
Although HS is an inammatory skin disease,
wound care is important in the treatment.
Adjuvant therapy is an important aspect of this
highly disturbing disease, because it provides
both safe symptom management and patient
empowerment. Most patients are left to their own
initiatives due to lack of appropriate dressing
materials, and when patients present in wound
care clinics for treatment, they constitute a challenge for many.
References
1. Jemec GB. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158–64.
2. Sabat R, Jemec GB, Matusiak L, Kimbal AB, Prens
E, Wolk K. Hidradenitis Suppurativa. Nat Rev.
2020;6:18.
3. Von der Werth JM, Jemec GB.Morbidity in patients
with hidradenitis suppurativa. Br J Dermatol.
2001;144:809–13.
4. Hurley H. Dermatologic surgery, principles and
practice. In: Roenigk RK, Roenigk HH, editors.
Dermatologic surgery, principles and practice.
NewYork: Marcel Dekker; 1989. p.729–39.
5. van der Zee HH, de Ruiter L, van den Broecke DG,
Dik WA, Laman JD, Prens EP. Elevated levels of
tumour necrosis factor (TNF)-α, interleukin (IL)-1β
and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β. Br J Dermatol.
2011;164(6):1292–8.
6. Danby FW, Jemec GB, Marsch WC, von Laffert
M. Preliminary ndings suggest hidradenitis suppurativa may be due to defective follicular support. Br J
Dermatol. 2013;168(5):1034–9.
7. Mozeika E, Pilmane M, Nürnberg BM, Jemec
GB.Tumour necrosis factor-alpha and matrix metalloproteinase- 2 are expressed strongly in hidradenitis
suppurativa. Acta Derm Venereol. 2013;93(3):301–4.
8. Zarchi K, Dufour DN, Jemec GB. Successful treatment of severe hidradenitis suppurativa with anakinra.
JAMA Dermatol. 2013;149(10):1192–4.
9. Hazen PG, Hazen BP.Hidradenitis suppurativa: successful treatment using carbon dioxide laser excision and marsupialization. Dermatologic Surg.
2010;36(2):208–13.
10. Morgan WP, Harding KG, Hughes LE.A comparison
of skin grafting and healing by granulation, following
axillary excision for hidradenitis suppurativa. Ann R
Coll Surg Engl. 1983;65(4):235–6.
11. Chopra D, Anand N, Brito S, Coutts P, George R,
Kimball A, Kirsner RS, Alavi A and Lev-Tov Hadaar.
Wound Care for patients with hidradenitis suppurativa : recommendations of an international panel of
experts, J Am Acad Dermatol. 2023;89(6):1289-1292.
12. Ragozo NM, Masson R, Gillenwater TJ, Hsiao JL
SVY. Emerging treatment and the clinical trial landscape for hidradenitis suppurativa—Part II: procedural and wound care therapies. Dermatol Ther
(Heidelb). 2023;13:1699–720.
Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License (http://creativecommons.org/licenses/by- nc- nd/4.0/), which permits any noncommercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit
to the original author(s) and the source, provide a link to the Creative Commons license and indicate if you modied the
licensed material. You do not have permission under this license to share adapted material derived from this chapter or
parts of it.
The images or other third party material in this chapter are included in the chapter's Creative Commons license,
unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons
license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to
obtain permission directly from the copyright holder.
Martorell Hypertensive Ischemic Ulcer
SylvieMeaume andHesterColboc
28
Martorell hypertensive ischemic ulcer, also called
necrotic angiodermatitis (NA), represents a particular type of leg ulcer with a specic clinical
presentation, histopathological appearance, and
therapeutic management. Its origin is independent of an underlying venous or arterial pathology, but, on the other hand, it is linked to the
deleterious action of arterial hypertension on the
cutaneous microvascularization. NA was mentioned for the rst time in 1945 by Martorell, a
Spanish cardiologist who described the rst clinical cases and observed the relationship with arterial hypertension [1].
28.1 Epidemiology
NA is not an exceptional condition (9–15% of leg
ulcers) [2–4] but is often overlooked and poses
problems of differential diagnosis with calciphylaxis, pyoderma gangrenosum, and certain vasculitis. The female sex seems predominant
(61–70%) [2, 3] with an age usually above
60years [2, 4]. Hypertension is present in nearly
100% of cases, diabetes in 30–50%, and chronic
smoking in 20% of cases [4].
S. Meaume (*) · H. Colboc
Department of Geriatric and wound care, Rothschild
University Hospital, Assistance Publique Hôpitaux de
Paris, Sorbonne Université, Paris, France
e-mail: sylvie.meaume@aphp.fr
28.2 Etiopathogenesis
The pathophysiology of NA is not fully elucidated at present. The invivo vascularization of
NA was compared to that of arterial ulcers using
a scintigraphic method [5]. Lower tissue perfusion than in patients with arterial disease has
been identied and explained by increased arteriolar resistance. This hypoperfusion would be
responsible for local ischemia and necrosis.
In another pathogenetic hypothesis, NA would
be a “cutaneous vascular accident” caused by
hypotensive episodes in patients on polymedicated therapy for their arterial hypertension
and with a pathological arteriolar network [6].
Finally, other authors put forward a hypothesis of paradoxical hypercoagulation phenomena,
in a context of anticoagulation with antivitamin
K [4].
28.3 Clinical Diagnosis
NA has a characteristic monomorphic clinical
expression, but there is a diagnostic delay of several weeks. It has a sudden post-traumatic onset
in 25–50% of cases [3, 4]. The onset is a purplish
macula, a bulla, or a hemorrhagic crust with a
purpuric periphery, which rapidly transforms into
a supercial necrotic plaque with characteristic
jagged and livedoid inammatory edges of variable sizes between 10 and 20cm2 (Fig.28.1). The
extension of this supercial ulcer is rapid
© The Author(s) 2024
L. Téot et al. (eds.), Skin Necrosis, https://doi.org/10.1007/978-3-031-60954-1_28
199
200
ab
Fig. 28.1 (a) NA in the early stage of necrosis (b) NA with central wound and peripheric necrosis
S. Meaume and H. Colboc
The preferential location of the NA is the
lower third of the leg. The lesions can be single or
multiple, and sometimes bilateral and symmetrical. Variable inammatory outbreaks with serpiginous ulcerative extension may follow one
another with the appearance of satellite elements.
Changes in position, lowering of the limb, rest, or
elevation, do not relieve the pain, which is an
important semiological element. A deep evolution with necrosis of the subcutaneous tissues
down to the muscle fascia and exposure of the
Fig. 28.2 Characteristic livedoid skin around NA
necrosis
tendons is possible but rare, mainly the Achilles’
tendon (13% of patients) [3]. Distal arteriopathy
is not usually hemodynamically signicant but
can accompany NA in 40% of cases as comorbidity. Chronic venous insufciency can be associated in 25–40% of cases and has to be managed
with compression bandages if ankle-brachial
pressure index is correct [4]. Spontaneous evolution of NA is towards stabilization and then
regression centripetal. A scar is sometimes visible after spontaneous regression of the lesions.
28.4 Histopathology
Fig. 28.3 NA : extensive supercial necrosis
(Figs.28.2 and 28.3). The ulcers are spontaneously hyperalgic and usually require quick transfer to a hospital to manage pain. The painful
character with paroxysms is an essential element
of the diagnosis.
Biopsy is not mandatory if the clinical diagnosis
is certain [2]. The histological picture is not specic but allows a diagnostic orientation. Above
all, it makes it possible to eliminate a differential
diagnosis. It is recommended to perform a skin
biopsy in an area of normal skin at the periphery
ab
28 Martorell Hypertensive Ischemic Ulcer
201
Fig. 28.4 Histopathology of NA, hematoxylin–eosin–
saffron stained: (a) arteriolosclerosis with reduction of
lumen of subcutaneous arterioles in NA. (b)
of the ulceration and at the level of the area of
necrosis. If a biopsy is performed in the necrosis,
deep and extensive hemorrhagic crust associated
with arteriolar and venular thrombosis can be
observed. If a peri-ulcer biopsy is performed, it
shows unspecic thickening of the media of
small-caliber arterioles and muscular arteries in
the dermis and hypodermis (arteriolosclerosis of
dermal vessels) (Fig.28.4).
Arteriolosclerosis with asymmetrical brous intimal
thickening, here associated to calcication of the internal
elastic lamina and media (courtesy of Dr Moguelet)
nation with neutrophil-rich dermal inltration
and signs of vasculitis. Any mechanical cleansing
is prohibited due to the phenomena of pathergy.
Calciphylaxis, also called calcium arteriolopathy, is a rare pathology associated with high
morbidity that most often appears in the context
of end-stage chronic renal failure in a dialysis or
transplant patient. It is characterized by the association of vascular calcications related to a
phosphocalcic imbalance, with cutaneous necrosis. The clinic is marked by the appearance of
28.5 Dierential Diagnoses
indurated and painful livedoid plaques with livedoid purpura and deep central necrosis within the
NA poses problems of differential diagnosis with
other vascular diseases. Diagnosis is usually
based on the characteristic clinical appearance in
the absence of underlying venous or arterial etiology, except in cases where these conditions may
be associated. Extreme pain and skin necrosis
exclude the diagnosis of venous ulcer, and the
absence of claudication and supercial trophic
disorders is not in favor of an arterial ulcer.
Pyoderma gangrenosum is differentiated from
NA by the presence of peripheral purulent pits,
sunken “mined” edges, and cribriform scars, as
well as a characteristic histopathological exami-
plaques. Cutaneous lesions have a predilection
for regions rich in adipose tissue such as the
abdomen and the root of the thighs in the proximal form of uremic calciphylaxis. Less commonly, they appear on the legs, constituting the
distal form of uremic calciphylaxis [3]. A variant
of non-uremic calciphylaxis has been described,
in the absence of renal or parathyroid pathology,
but is on the other hand often associated with two
cardiovascular risk factors: arterial hypertension
and diabetes. Patients may have other serious
comorbidities such as cancers or hepatic cirrhosis. The clinic is also marked by extensive, deep,
202
bc
ab
S. Meaume and H. Colboc
and hyperalgesic necrotic lesions of the abdomen,
breasts, or thighs. Treatment is difcult, and mortality is high: 40–60% of cases [3].
The other differential diagnoses are thrombosing conditions (cryoglobulinemia, antiphospholipid syndrome, thrombophilia, etc.), cutaneous
vasculitis, and infectious or drug-induced ulcers.
28.6 Evolution
The evolution can be marked by successive outbreaks with recurrences in 60–80% of cases.
These occur in other territories or on the contralateral limb. The local prognosis is on the other
hand rather favorable, with the rate of amputation
being less than 1%.
28.7 Treatment ofNA
1. The use of analgesics is essential not only for
the comfort of the patient but also for a better
realization of the care. Although skin grafting
remains the main means of relieving the
patient, the patient should generally be administered WHO level II or III analgesics as soon
as possible. The use of morphine is often necessary and must be quickly instituted.
Neuropathic analgesic treatments can be associated (pregabalin, tricyclic antidepressants)
because of the neuropathic component associated with the pain of NA.Faced with pain that
is resistant to conventional medical treatments, the use of nitrous oxide at the time of
care and the use of nerve blocks via a perineural catheter may be necessary.
2. Skin grafts (Figs.28.5 and 28.6) currently repre-
sent the “gold standard” of NA treatment. This
benecial therapeutic effect of skin grafting was
described in 1995 [7]. This involves pinch skin
graft or mesh graft, performed after mechanical
or autolytic debridement of necrotic tissue. They
must be carried out as soon as possible when the
diagnosis is evoked. The common results
obtained on the grafts in the NA conrm the
effectiveness on pain with analgesic withdrawal
in 8days, disappearance of the peripheral pur-
a
Fig. 28.5 Pinch graft procedure: (a) preparation of the donor site (inner side of the thigh) and of the material. (b) Grafts
harvesting. (c) Grafts placement
Fig. 28.6 Evolution of pinch graft on a typical NA. (a) Before pinch graft. (b) Day 4 pinch grafts
28 Martorell Hypertensive Ischemic Ulcer
203
plish halo in 8 days, and complete healing in
30–45 days on average. This effectiveness is
demonstrated if the transplants are early and
repeated (ref à ajouter) [3, 8, 9].
3. Wound care, as an alternative treatment of
NA, is centered on the autolytic debridement
of the cutaneous necrosis, and using suitable
dressings such as hydrogels, irrigoabsorbents,
alginates, or hydrobers, depending on the
degree of exudate and the quality of the surrounding skin of the wound, can be proposed.
Strong to very strong local topical corticoste-
roids used around the ulcer on the inamed
areas in the absence of signs of local infection
are prescribed in order to reduce the extension
of the lesion. Electrostimulation techniques
have been proposed in the NA.They allow a
debridement of necrotic and brinous wounds
and above all have an analgesic effect [10].
Negative-pressure therapy has been proposed
pre- or post-skin graft [3]. However, medical
measures alone only allow healing in 6% of
cases according to Hafner et al. [3] and
10–25% of cases according to Senet [11],
which underlines the fundamental role of skin
grafting in the treatment of NA.
28.8 Other Treatments
The preventive measures of NA essentially concern the control of arterial pressure, which should
not vary too much over time. In case of association with venous insufciency, compression bandage must be associated. It also stabilizes the
grafts and often allows faster healing. Cessation
of smoking and nonselective beta-blockers is
often recommended [2].
28.9 Conclusion
NA is a non-exceptional cause of leg ulcer but too
often overlooked and often leads to late diagnosis. It is a very painful arteriolar ulcer, difcult to
treat and which has a negative impact on the
patient’s quality of life. Management is based on
pain management, blood pressure control, and
mechanical or autolytic debridement followed by
skin grafting.
References
1. Martorell F. Las ulceras supramaleolares por arteriolitis de las grandes hipertensas. Actas (Reunion
Cientica Cuerpo Facultad). Instituto Policlinico
Barcelona. 1945;1(1):6–9.
2. Vuerstaek JDD, Reeder SWI, Henquet CJM, H. a.
M.Neumann. Arteriolosclerotic ulcer of Martorell. J
Eur Acad Dermatol Venereol. 2010;24(8):867–74.
3. Hafner J, Nobbe S, Partsch H, Läuchli S, Mayer D,
Amann-Vesti B, Speich R, Schmid C, Burg G, French
LE. Martorell hypertensive ischemic leg ulcer: a
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G. Retrospective study of hypertensive leg ulcers
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5. Duncan HJ, Faris IB.Martorell’s hypertensive ischemic leg ulcers are secondary to an increase in the local
vascular resistance. J Vasc Surg. 1985;2(4):581–4.
6. Saadallah S, Couillet D, Richard M, Vaisse B,
Guillaume JC, Grob JJ, etal. L’angiodermite nécrotique, un « accident vasculaire cutané » par hypotension brutale sur une artériolopathie hypertensive ?
Étude ouverte prospective preliminaire. Annales de
Dermatologie et Venereologie. 2000;127:4S8-9.
7. Lazareth I, Priollet P. Necrotic angiodermatitis:
treatment by early cutaneous grafts. Ann Dermatol
Venereol. 1995;122(9):575–8.
8. Dagregorio G, Guillet G.A retrospective review of 20
hypertensive leg ulcers treated with mesh skin grafts. J
Eur Acad Dermatol Venereol. 2006 Feb;20(2):166–9.
9. El Khatib K, Danino A, Rzin A, Malka G. Necrotic
angiodermatitis: evaluation of an early skin graft
treatment. Ann Chir Plast Esthet. 2009;54(6):567–70.
10. Leloup P, Toussaint P, Lembelembe JP, Célérier P,
Maillard H. The analgesic effect of electrostimulation (WoundEL®) in the treatment of leg ulcers. Int
Wound J. 2015;12(6):706–9.
11. Senet P, Vicaut E, Beneton N, Debure C, Lok C,
Chosidow O. Topical treatment of hypertensive
leg ulcers with platelet-derived growth factor BB: a randomized controlled trial. Arch Dermatol.
2011;147(8):926–30.
204
Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License (http://creativecommons.org/licenses/by- nc- nd/4.0/), which permits any noncommercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit
to the original author(s) and the source, provide a link to the Creative Commons license and indicate if you modied the
licensed material. You do not have permission under this license to share adapted material derived from this chapter or
parts of it.
The images or other third party material in this chapter are included in the chapter's Creative Commons license,
unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons
license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to
obtain permission directly from the copyright holder.
S. Meaume and H. Colboc