Acne E-Book

F. William Danby

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 769

Veröffentlichungsjahr: 2014

Beschreibung

Learn to accurately diagnose, prevent and treat all three acnes using both traditional and novel approaches to understanding the causes and selecting the most effective treatments. 

Acne vulgaris is an extremely common condition. It is troublesome to manage, often persisting into middle age.  Exact causes are becoming clear and include several hormonal stimulants, some triggered by the Western diet, and a pathogen ignored for decades.  Acnes rosacea and inversa (hidradenitis suppurativa) are discussed from entirely new viewpoints.

Acne: Causes and Practical Management will provide readers at all levels with a practical, well-illustrated approach to fully understanding these disorders; a faster and more cost-effective management regimen and the rationales for their prevention. 

In full colour throughout and with over 200 excellent clinical images, key highlights include:

• Full coverage of all acne presentations – acne vulgaris, acne rosacea and acne inversa (hidradenitis suppurativa)
• An integrated view of the causes of the varied and overlapping acnes
• Preventive, novel and curative approaches to treatment
• Medical, surgical, and dietary components of management, fully integrated
• Highly practical focus on prevention, treatment and prophylaxis based on emerging pathogenetic concepts

Brought to you by one of the world’s leading authorities on the subject, Acne: Causes and Practical Management will be a valuable re-education for the dermatologist and all those who treat or suffer from these three conditions.

Leseprobe

CONTENTS

Cover

Title page

Copyright page

Preface

Practical acne therapy

Genetics

Diet

Hormones

Stress

Comedones (plugs in pores)

Blemishes—a brief catalogue

Nodules

Scars and sinuses

Support

Introduction

Nomenclature

The three acnes and grading

References

Chapter 1: The three acnes and their impact

1.1 Acne vulgaris

1.2 Acne rosacea

1.3 Acne inversa (formerly hidradenitis suppurativa)

1.4 The psychology of acne

References

Chapter 2: The folliculopilosebaceous unit—the normal FPSU

2.1 Anatomy

2.2 Genetics

2.3 Epigenetics

2.4 Embryology

2.5 Histology

2.6 Physiology

2.7 Biochemistry

2.8 Hormones, enzymes, receptors, and the intracrine system

2.9 FoxO1 and mTORC1

References

Chapter 3: Pathogenetic mechanisms summarized

3.1 Acne vulgaris

3.2 Acne rosacea

3.3 Acne inversa/hidradenitis suppurativa (AI/HS)

3.4 Other variants

References

Chapter 4: The acne hormones

4.1 The endogenous hormones

4.2 The exogenous hormones

References

Chapter 5: Exogenous acnegens and acneform eruptions

5.1 Chemicals and medications

5.2 Endocrine imitators and disruptors

5.3 Foods

5.4 Photodamage, glycation, and the acne and aging processes

5.5 Smoking and nicotine

References

Chapter 6: Follicular flora, fauna, and fuzz

6.1

Propionibacterium acnes

(

P. acnes

)

6.2

Malassezia

species

6.3 Staph, strep, and gram-negative organisms

6.4 Demodex

6.5 Vellus hairs

References

Chapter 7: The inflammatory response

7.1 Innate immunity

7.2 Adaptive (acquired) immunity

7.3 Inflammation as the primary acnegen

7.4 Mediators, cellular and humoral, and neuroimmunology

7.5 Allergy (shared antigens)

7.6 Inflammation, pigment, and PIH

7.7 Inflammation and scarring

References

Chapter 8: Management

8.1 Prevention

8.2 General principles of management

8.3 Diet

8.4 Comedolytics and other topicals

8.5 Anti-inflammatories and antimicrobials

8.6 Hormone manipulations and therapy

8.7 Surgery

8.8 Lights and lasers

References

Chapter 9: Acne in pregnancy

9.1 Epidemiology

9.2 Pathogenesis

9.3 Team up with Mother Nature

9.4 Targeting therapy

9.5 Discussion

9.6 Summary and conclusion

References

Chapter 10: Putting it all together

10.1 Lifestyle choices and the acnes

10.2 Therapeutic choices and the acnes

10.3 Conclusion

References

Chapter 11: Appendices

11.1 Appendix A: the rosacea “classification and staging” controversy

11.2 Appendix B: the dairy versus carbohydrate controversy

References

Chapter 12: The handouts

12.1 Acne

12.2 The “zero-dairy” diet

12.3 The risks and benefits of isotretinoin

12.4 The Paleo diet

12.5 Acne inversa / Hidradenitis suppurativa (AI/HS)

12.6 Yasmin/Ocella/Zarah or Yaz/Gianvi extended cycle for acne therapy

Index

End User License Agreement

List of Tables

Chapter 04

Table 4.1 Progestins vary, the more androgenic make acne worse, the less or non-androgenic prevent and clear acne.

Table 4.2 Changes in growth and dairy consumption in Japan, 1950 and 1975.

Chapter 08

Table 8.1 Spironolactone side effects.

Table 8.2 Spironolactone interactions.

List of Illustrations

Practical-acne-therapy

Figure 0.1 Classic open non-inflamed comedones with early inflammation just starting.

Figure 0.2 Mainly closed comedones with occasional “blackheads.”

Figure 0.3 Central facial folliculopapules and folliculopustules, with no comedones and minor background erythema.

Figure 0.4 These little nodules were the only clue to the disease. Family history was positive.

Figure 0.5 Retinol is the classic vitamin A. Tretinoin, also called

vitamin A acid

and

retinoic acid

, was first marketed as Retin-A®.

Figure 0.6 Isotretinoin, which is now widely genericized, was originally marketed as Accutane® and Roaccutane®. Acitretin started life as a treatment for psoriasis.

Figure 0.7 Comedones and folliculopapules in juvenile acne. His hormone source was dairy on top of a positive family history.

Figure 0.8 Papulopustules with a pustulonodular lesion centrally. She was on an androgenic oral contraceptive and enjoyed her dairy.

Figure 0.9 Secondary culture-positive staphylococcal pustule superimposed upon folliculopustular acne.

Figure 0.10 Nodular lesions occur even in juvenile acne.

Figure 0.11 Early inflamed nodule on lateral mons pubis, with surrounding scars and tombstone comedones.

Figure 0.12 Acne rosacea with inflamed facial nodules.

Figure 0.13 Upper inner thigh lateral to inguinal crease showing several interconnected acne inversa nodules, some bleeding to the surface.

Figure 0.14 Active acne vulgaris showing nodules and pustules ready to drain and areas of subsequent scarring.

Figure 0.15 Indurated acne inversa/hidradenitis suppurativa lesion being unroofed and showing an ovolinear gelatinous mass in the base of the wound and a dilated epidermoid cystic component of a tombstone comedo with no pilar (hair root) and no sebaceous gland material, attached to the underside of unroofed material.

Figure 0.16 Acne inversa/hidradenitis suppurativa of scrotum with purulent secondary infection.

Figure 0.17 Early folliculocentric scarring of individual follicular groups, with coalescence into hypertrophic scarring. These scars are not true keloids (extending beyond the area of injury), but the name is unlikely to be changed to acne hypertrophicus.

Figure 0.18 Residual hypertrophic and early keloidal shoulder scars following clearance with isotretinoin.

Introduction

Figure 0.19 Wax models (

moulages

) of acne vulgaris originally in Neisser’s Clinic in Breslau, now the Museum of Moulages (Muzeum Mulaży) of the Department of Dermatology in Wrocław (Breslau), Poland. From Jacobi-Pringle. Models in Neisser’s Clinic in Breslau.

Figure 0.20 The folliculopilosebaceous unit (FPSU) is composed of three distinct structures: the follicular unit, the sebaceous unit, and the pilar unit. The follicular unit (through which the hair shaft and sebum reach the surface) starts at the surface as the acroinfundibulum (the upper portion of the follicle as it penetrates the epidermis) and continues as the infrainfundibulum to the isthmus where the sebaceous glands join the follicular unit and empty sebum into the follicular canal. The necks of the sebaceous glands that form the sebaceous unit attach through the sebofollicular junction area to the isthmus. Deep to (and continuous with) the isthmus is the pilar unit. The hair produced by the pilar unit in acne vulgaris, acne rosacea, and acne inversa/hidradenitis suppurativa may be so small that it is not apparent in biopsies of the FPSU. The bulge area is a thickened area of the upper pilar unit, just below the bottom of the isthmus–sebofollicular junction area. It is the source of the stem cells that repopulate injured epidermis, hair, and sebaceous glands. The FPSU illustrated is likely from the scalp of someone with fair hair.

Figure 0.21 Folliculopilosebaceous unit with detail and orientation of the sebofollicular junction area. The black oval shows the top and bottom limits of the isthmus section of the pilofollicular tube. The necks of the sebaceous glands that “plug into” the isthmus through 360° form the sebofollicular junction. The bulge area is likewise a 360° wrap around the upper portion of the pilar unit. It is composed of a series of stem cells—the ones closest to the sebofollicular junction are Lgr6 type and may be the source of the invasive proliferative gelatinous mass (IPGM), which is to be further discussed in this book. From http://upload.wikimedia.org/wikipedia/commons/7/7c/Insertion_of_sebaceous_glands_into_hair_shaft_x10.jpg.

Figure 0.22 Plewig’s Follikel-Filament—the earliest form of follicular plugging, with compact pink lamellae of lining keratinocytes, a fine hair that is barely visible, and purple colonies of anerobic

Propionibacterium acnes

. Note that the

stratum corneum equivalent

and the intraductal keratin layer near the hair at the top end are thin and loose, indicating that terminal differentiation and desquamation are occurring normally. From

Acne and rosacea

, 2e, Kligman, Albert M; Plewig, Gerd.

Figure 0.23 The early comedo starting to accumulate deep in the infrainfundibular part of the follicular unit, showing thickening of the stratum corneum underlying multilayered compact keratin as terminal differentiation fails. From

Acne and rosacea

, 2e, Kligman, Albert M; Plewig, Gerd.

Figure 0.24 Closed comedones do have an opening to the surface, but it is too tight to permit the compacted keratin in the dilated follicular unit to exit. The content may become large enough that the structure is called an

epidermoid cyst

. The term

sebaceous cyst

is a misnomer—the sebaceous glands are normally “squeezed out” to the point that they are rarely detected in these structures. From

Acne and rosacea

, 2e, Kligman, Albert M; Plewig, Gerd.

Figure 0.25 Open comedones are not static plugs in the follicle. New keratinocytes are added to their outside layer, and the central keratinocytes are slowly lost through the follicular opening. From

Acne and rosacea

, 2e, Kligman, Albert M; Plewig, Gerd.

Figure 0.26 The rupture in the wall of this follicular unit has allowed intraductal material to escape, causing the surrounding peri-follicular inflammation and allowing inflammatory cells to enter the duct.

Figure 0.27 Inflammatory papular, pustular, nodular, and scarring acne coexisting with extensive non-inflammatory comedonal acne.

Figure 0.28 The exaggerated webbed scarring that can occur in acne inversa/hidradenitis suppurativa, as in this right armpit/axilla, can be destructive and invasive instead of a healing influence.

Figure 0.29 Acne rosacea is basically a folliculocentric inflammatory reaction directed at material in the follicular duct. The inflammation varies in depth and degree depending upon the variable content of the pore, the varied immune responses of the patient, and the varied therapies undertaken. This woman failed to respond to topical metronidazole and oral tetracycline group antibiotics but cleared with combined therapy directed at

Demodex

and

Malassezia

.

Figure 0.30 These very superficial folliculopustules are the hallmark of

Demodex

involvement in acne rosacea.

Figure 0.31 This is acne rosacea under treatment with a somewhat irritating, drying, elemental precipitated sulfur and sulfonamide antibiotic topical lotion. Part of the redness is from irritation, some is from the inflammation of the follicles, and some from underlying dilated blood vessels.

Figure 0.32 The rosy background glow of dilated superficial venules and capillaries gives acne rosacea its name. Most of the dilation of the vessels is due to actinic (from the sun) damage to the support structures of the vessels, allowing them to dilate and contain more red blood cells. This actinic telangiectasia may stand alone or may be left behind, as in this case, when the acne rosacea is cleared.

Figure 0.33 This man’s rhinophyma involved only the bulb of the nose. It responded to nothing but low-dose oral isotretinoin over several months. The undelying fibrosis has left him with a prominent nasal bulb, but it is much improved from the original bright-red swollen condition.

Figure 0.34 This is ocular rosacea. Note the residual conjunctival telangiectasia and cheimosis (edema) despite active treatment.

Figure 0.35 A classic location for acne inversa/hidradenitis suppurativa, deep in the left inguinal (groin) crease where friction and pressure combine to rupture the folliculopilosebaceous unit structure at its weak points.

Figure 0.36 In addition to classic acne inversa/hidradenitis suppurativa and acne vulgaris lesions elsewhere, this man suffered from a lifetime of scarring ruptured epidermoid cysts.

Figure 0.37 The characteristic invasive inflammatory material traveling horizontally just below the skin surface produces this type of indolent invasive linear scarring.

Figure 0.38 In the sacral area, acne inversa/hidradenitis suppurativa is often recurrent due to sitting pressure, and the invasive mass and sinuses are often forced deep by such pressure.

Figure 0.39 Hair follicles, when involved in acne inversa/hidradenitis suppurativa, take the inflammation to new depths. The result can be permanent hair loss if the hair bulb and stem cells are destroyed.

Figure 0.40 Scars like this are heartbreaking to patient and dermatologist alike—so preventable if treated early. Her mother would not permit any oral medication and insisted that consuming lots of healthy dairy foods would help her “grow out of it.”

Chapter 01

Figure 1.1 (A) The first tiny accumulation of the lining cells, the keratinocytes, in the follicular duct. (B) Accumulation of these flat cells in the follicle leads to the microcomedo.

Figure 1.2 Acne rosacea loves convex, sun-exposed skin with a healthy population of well-stimulated FPSUs.

Figure 1.3 Some dermatologists consider this “pre-rosacea.” Close inspection reveals a few comedones—almost normal in a 15 year old. He needs lifelong, truly broad-spectrum sun protection to prevent worsening of his actinic telangiectasia; a dairy-free diet; and a gentle topical retinoid.

Figure 1.4 Longstanding sun exposure gradually weakens the collagen and other support tissues that wrap around and support the blood vessels, allowing them to dilate. The blood pools in them and turns dark, as on this man’s nose.

Figure 1.5 Longstanding sun exposure gradually weakens the collagen and other support tissues that wrap around and support the follicular units, allowing them to dilate. The keratin and some sebum pool in them, and some even turn dark, as on this man’s cheek.

Figure 1.6 This family of adult, juvenile, and a baby Demodex mite had occupied a pustule on the forehead of a rosacea patient. The background shows pus and a keratinous plug (plus some round air bubbles).

Figure 1.7 The innate immune system reacts to ingrown hairs, likely even the tiny ones like this, caught in a keratinous plug in a folliculopustule in acne rosacea.

Figure 1.8 Instead of using the olive oil overlay, the nutritional requirement of

Malassezia

is met in Dixon’s agar by including glycerol mono-oleate. From http://www.mycology.adelaide.edu.au/gallery/yeast-like_fungi/

Figure 1.9 Note the variation in the thickness of the PAS+ (periodic acid–Schiff positive) support material, 2–3+ on the outside of the pilar unit (black oval) and 1/2 to 1 1/2+ on the inner aspect of the sebofollicular junction (white oval).

Figure 1.10 The short arrows show periodic acid–Schiff (PAS) 2+ and no inflammation; the long arrows show PAS 0–1+ and active inflammatory infiltrate.

Figure 1.11 Double white arrows show areas of destruction, with smudged scarred collagen. The short black arrow shows a diminished residual sebaceous unit. The long black arrow indicates a pilar papilla under destruction.

Figure 1.12 The uninflamed healthy collagen on either side of this half-destroyed sebofollicular junction provides evidence of the specificity of the inflammatory attack. No sebaceous gland remains.

Figure 1.13 The outline of the residual parts of the pilar unit is just barely visible.

Figure 1.14 Despite the intense inflammatory activity nearby, the apocrine glands show no structural damage.

Figure 1.15 Note the red tender area (white arrow) with no comedo and the tombstone comedo (black arrow) next to it.

Figure 1.16 Excision site placed to remove both inflamed lesion and tombstone comedo.

Figure 1.17 This is actually the first of several lesions, some of them communicating, that involve this left inguinal crease.

Figure 1.18 A simple oval cut with scissors cleared the area nicely. Further extensive work was needed to the left, inferomedial to this lesion.

Figure 1.19 The stem cells that form the bulge migrate from the deeper part of the bulge upward toward the sebofollicular junction, and their characteristics and potentials change as they move “north.” The stem cells bearing the Lgr6 marker (in yellow) are, at the time of writing, the best candidates for producing the epithelialized sinuses that represent the FPSU’s attempt to heal.

Figure 1.20 This biopsy was taken early in the development of a single lesion, and was done with a 6 mm punch. The material recovered contained a localized area of gelatinous material at the lower right in addition to the fragment of exploded FPSU and the intense inflammatory activity located more superficially.

Figure 1.21 Scattered throughout this loose gelatinous matrix are several cell types, including keratinocytes, inflammatory cells, evolving new capillaries, and about 20 little round bundles of cells that are suspected to be “activated keratinocytes,” likely of stem cell origin, likely from the Lgr6+ population, and the likely source of the small structures in Figures 1.23 and 1.24.

Figure 1.22 The difference in morphology between the newly formed capillary (right central) and the other little round bundles of cells is apparent. Marker studies to accurately identify these structures are under way.

Figure 1.23 The central structure is apparently the precursor of the sinus tracts. Its first chore appears to be the fabrication of a protective barrier of PAS+ (periodic acid–Schiff positive) material. This is obvious centrally (white arrow), but on closer observation one can see several other younger structures (likely evolved from the “little round bundles”) showing faint early PAS+ barrier development (red arrows).

Figure 1.24 The structure appears to be no accident. The remarkably PAS+ (periodic acid–Schiff positive) cells in the center are a feature of the pilofollicular structure. See Figure 1.12 and the bulge area in Figure 1.19.

Figure 1.25 The protective PAS+ (periodic acid–Schiff positive) layer has allowed coalescence of several of the primordial sinus structures. Note the outer PAS+ material, the basal cell layer, the acanthotic “epidermoid” sinus lining, and the immature but recognizable laminated keratin, all under development.

Figure 1.26 The PAS+ (periodic acid–Schiff positive) layer is better developed, now a healthy and protective 3+; the epidermoid lining is better defined; a stratum granulosum has developed; and the keratin is truly laminated.

Figure 1.27 This indolent lesion had been present for months. Note the invasive proliferative gelatinous mass (IPGM) at the base.

Figure 1.28 Clean healthy base. This tissue wants to heal; it just needs to be given the opportunity. Ferric chloride and petrolatum normally heal such wounds in about 10–14 days.

Figure 1.29 The lesion was uncomfortable, was not as painful as it had been, and was not as swollen, but it “just won’t go away and keeps getting bigger.”

Figure 1.30 Not a drop of purulent material was released, a useful condition most likely attributable to the adalimumab.

Figure 1.31 Looks pretty clean. Maybe just a little ferric chloride and petrolatum, and that’s all that is needed?

Figure 1.32 Looks like there is something else here besides pus or keratinous debris.

Figure 1.33 This is not keratin, it is not pus, it is not granulation tissue, and it is not fat. This is the invasive proliferative gelatinous mass (IPGM).

Figure 1.34 Here is the clean base of the lesion: uninfected dermis that will heal beautifully with nothing more than petrolatum.

Figure 1.35 This very tender lesion was about 2 cm × 5 cm. It was a much more impressive red before the local anesthetic was placed.

Figure 1.36 The purulent drainage is a reliable indicator of the degree of pain.

Figure 1.37 Under the purulent material, there is characteristic invasive proliferative gelatinous mass (IPGM).

Figure 1.38 These were both incised and drained (I&D’d) about 5 days prior with simple stab wounds. Note the profusion of plugged pores in this inframammary area.

Figure 1.39 This is the top of the specimen removed using a punch biopsy, about a week after the patient had had an I&D in the emergency room. Note the residual mass of actively growing keratinocytes trying and failing to repair the ruptured FPSU. The inflammatory infiltrate that was producing the swelling and pain is obvious; indeed, beneath this there was significant abscess formation and foreign body reaction.

Figure 1.40 The red arrows illustrate the traditional link between stress, the corticotropin-releasing hormone (CRH) it stimulates, and acne. The green arrow illustrates what is now considered the “shortcut.” Just to make life interesting, CRH receptors are also present on eccrine sweat glands (that may be linked to the sweaty palms and soles caused by stress), and the FPSU seems to be capable of making its own CRH in its own intracrine system.

Chapter 02

Figure 2.1 The follicular unit consists of the intraepidermal acroinfundibulum (A), the intradermal infrainfundibulum (B) that extends to the top end of the isthmus (C), and then continues as the pilar unit (D) containing the hair papilla and follicle. The sebaceous unit is composed of all the sebaceous glands that join the isthmus (C) at the sebofollicular junction (E). It is a 360° structure that wraps around the isthmus.

Figure 2.2 We have more natural sebaceous gland activity at birth than at any other time of life. The sebum and water mix called

vernix caseosa

is what lubricates our way into the world.

Figure 2.3 The periodic acid–Schiff positive (PAS+) structure that separates the epidermis above from the dermis below is generally homogeneous and well formed, as is the similar material investing vascular and other appendageal structures.

Figure 2.4 Note the well-defined periodic acid–Schiff positive (PAS+) support to the right wall, with no inflammation. On the left, there is marked destructive inflammation from 6 to 9 o’clock, where a sebaceous gland has only a small stump left.

Figure 2.5 Despite the destructive inflammation applied to the sides of the upper portion of this pilar structure, just below the isthmus, there is little to no involvement of the eccrine ducts on the right—hiding effectively behind their periodic acid–Schiff positive (PAS+) protective wrap. Note that the sebaceous glands have been reduced to stumps.

Figure 2.6 These apocrine glands exist in a sea of inflammatory cells, with no suggestion that they are the focus of the activity. There are one or two inflammatory cells beginning to push past the strong periodic acid–Schiff positive (PAS+) protection at 4–5 o’clock on the left and at 6:30 o’clock on the right, substantiating the concept of their secondary involvement.

Figure 2.7 The basement membrane (shown as pink under the epidermis) wraps around the whole folliculopilosebaceous unit, like a vinyl glove. Anything above the pink layer, and anything within the vinyl glove equivalent, is considered “non-self” or “foreign” by the inflammatory guardians of the integrity of the inside “self” area.

Figure 2.8 The pressure produced within the duct is such that the keratinocytes, unable to separate from each other, are thrown into folds within the strained confines of the follicular duct.

Figure 2.9 This sebaceous gland is cut in cross-section in an area away from the sebofollicular junction and shows a healthy periodic acid–Schiff positive (PAS+) support structure and a minimal population of tissue-resident immunocytes.

Figure 2.10 The sebaceous unit plugging into the isthmus of the pilofollicular structure. Note there is no free sebum pool—the sebocytes dissolve only upon contact with the hair. Note the inflammation concentrated where minimal periodic acid–Schiff positive (PAS+) material is present at 6–6:30 and 7–9 o’clock and one or two inflammatory cells at 3 o’clock.

Figure 2.11 The failure of the keratinocytes to achieve terminal differentiation, likely due to anoxia and mediated by hypoxia-inducible factor 1 (HIF-1), leaves behind the lipids that would have been used as structural lipids or as a source of energy to fuel the differentiation.

Figure 2.12 The intracrine system utilizes five onsite enzymes to produce the range of androgens needed in and around the folliculopilosebaceous unit and elsewhere in the body. Some may be made directly from cholesterol; others may utilize the androgen precursors in dairy products.

Figure 2.13 The gray dustlike formazan particles sprinkled in the keratinocytes of the ductal wall (top arrow) and concentrated in a sebocyte (bottom arrow) indicate the location of the enzyme 17β-hydroxysteroid dehydrogenase (17β-OHSD in Figure 2.12). From PhD thesis, 1970.

Figure 2.14 This diazo slide made from Calman’s original paper illustrates the earliest expression of the present concept of hormonally driven acne. From PhD thesis, 1970.

Figure 2.15 Regulation of mTORC1 is the final common pathway to increased lipids (sebaceous) and active protein (ductal plugging cell) activity. From: Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne. Bodo C. Melnik and Christos C. Zouboulis.

Experimental Dermatology

, 2013, 22, 311–315.

Figure 2.16 The chain of events from diet to plugged duct is simplified here.

Chapter 03

Figure 3.1 The chain of events from keratinocyte excess to medical and surgical management of the plugged and exploded duct is simplified here. Excess keratinocyte production begets the early plug that expands and triggers the anoxia that, likely through hypoxia-inducible factor 1, interferes with terminal differentiation and induces inflammation.

Figure 3.2 The central third of this image shows new scarring and residual inflammation centered on an area where a sebaceous gland has been destroyed, leaving behind the ragged stub of the sebofollicular junction still attached to the isthmus area of the follicle. The nearby apocrine ducts are well protected by their PAS+ (periodic acid–Schiff positive) wrap, while inflammatory cells are still present, attacking the areas of the follicular wall unprotected by PAS+ material at 4–5 and 9–10 o’clock.

Figure 3.3 Beneath a tombstone comedo. As the sole surviving portion of a folliculopilosebaceous unit that has undergone explosive destruction, the intact residual follicular component, still under the influence of the hormones of growth, continues to produce lamellae of keratin that have difficulty exiting the pore.

Figure 3.4 As elsewhere, the inverse and deep involvement is a challenge to manage. Surgical I&D (incision and drainage) is best avoided on the face but is sometimes unavoidable, leaving incisional scars, residual activity and epidermoid cystic inclusions.

Figure 3.5 AI/HS buttock (1), initial presentation: September 2010. This degree of involvement might attract extensive surgical attention, but that is best avoided.

Figure 3.6 AI/HS buttock (2), March 20, 2013: Following confidence building with several smaller areas, this large area on the left hip and buttock was unroofed.

Figure 3.7 AI/HS buttock (3), March 25, 2013: With no dressing other than petrolatum, the wounds are clean and comfortable, causing minimal interference with office work, and without need for analgesia.

Figure 3.8 AI/HS buttock (4), November 18, 2013: Wounds are clean and dry. Petrolatum is still in use after baths or showers to combat dryness and avoid chafing.

Figure 3.9 Eight weeks of weekly pulsed oral ketoconazole will eliminate the yeast-induced lesions and leave the few closed comedones behind.

Figure 3.10 While there are a few comedones here, the monomorphous folliculopapules and folliculopustules extending into the scalp make the diagnosis.

Figure 3.11 Note the pigmentation and scaling, indicating coexisting pityriasis (tinea) versicolor.

Figure 3.12 A six-month course of doxycycline produced this “antibiotic-resistant acne.”

Figure 3.13 Dissecting terminal folliculitis. Note the deep inflammatory nodule and the numerous scars and pustules. This man also had draining nodules in the groin.

Figure 3.14 Acne keloidalis. Classic location with scarring alopecia, inflammatory drainage, and hypertrophic, folliculocentric scars.

Figure 3.15 EGFR inhibitor eruption. “Acneiform” pattern of eruption due to unknown mechanism.

Figure 3.16 EGFR inhibitor eruption. Initial presentation (not shown) cleared and stayed clear with ketoconazole orally while taking erbitux and irinotecan. Ran out of weekly 200 mg ketoconazole and flared over face, trunk, and limbs.

Figure 3.17 EGFR inhibitor eruption. November 2: Same flare, left forearm. Methicillin-resistant

Streptococcus aureus

positive, sensitive to sulfa (patient allergic) and vancomycin (avoiding because of previous diarrhea), and borderline sensitive to tetracycline. Restarted oral ketoconazole and topical neomycin ointment, and added minocycline when cultures available.

Figure 3.18 EGFR inhibitor eruption. November 10: Cleared and remained clear on 200 mg ketoconazole weekly until deceased five months later.

Figure 3.19 EGFR inhibitor eruption. Presented January 16 under treatment with brentuximab with rash on the xiphisternal area of two weeks. Started ketoconazole orally 400 mg in a single dose weekly. Topical petrolatum only.

Figure 3.20 EGFR inhibitor eruption. Essentially clear on January 23. Photo shows status on February 6 after a total of four tablets of 200 mg ketoconazole.

Figure 3.21 Brocq monograph of 1898.

Chapter 04

Figure 4.1 Peripheral conversion of androgens to estrogens. The ovaries are the major source of the estrogens in females; these pathways to E1, E2, and E3 are more important in males.

Figure 4.2 The green line at the 250 level gives a remarkably accurate “acne threshold” for both the prevalence and the timing of acne vulgaris.

Figure 4.3 This list comprises the exogenous anabolic androgenic steroids, the man-made or man-modified hormones used to enhance performance (or to treat some diseases). Some of the endogenous anabolic androgenic steroids (androstenediol, androstenedione, dihydrotestosterone, dehydroepiandrosterone [DHEA], and testosterone) may also be used by injection and are then considered exogenous.

Figure 4.4 The final effector, mammalian target of rapamycin complex 1 (mTORC), gives the green light to growth, causing the plugged pores that are at the root of all acnes plus the seborrhea that accompanies some varieties.

Figure 4.5 Patients appreciate the choice of the standard versus the extended BCP regimen.

Figure 4.6 If every women were to be tested, before starting hormonal contraceptives, for factor V Leiden, prothrombin II, and blood type—and if a clinical trial to check on the efficacy of 81 mg acetylsalicylic acid were to show a protective effect—lives could be saved. Meanwhile, personal and family history is all we can rely on.

Chapter 05

Figure 5.1 Victor Yushchenko (A) after TCDD exposure, and (B) at 5 years. (A) By Muumi (own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons. (B) By http://www.flickr.com/photos/maiakinfo/3664435519/JürgVollmer/maiak.info [CC-BY-SA-2.0 (http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons.

Figure 5.2 One out of four (the egg protein) isn’t bad!

Chapter 06

Figure 6.1

Malassezia

growing on the surface is unrecognized by the immune system at first, whether here on the skin surface or down in the pores. Once recognition occurs, this surface infection can become quite itchy and may become pale pink or red.

Figure 6.2 The pink inflammation of active

Malassezia

-induced tinea versicolor.

Figure 6.3 Once

Malassezia

in the pores is recognized by the immune system, an impressive immunological follicular inflammation starts.

Figure 6.4 The eruption is most active over the central back, where the sebaceous activity is at its highest.

Figure 6.5 Note that the skin between the folliculopapules is totally normal—no dry itchy scaling, asteatotic eczema, or atopic or contact dermatitis.

Figure 6.6 The pattern is folliculopustular on this central and lateral chest.

Figure 6.7 The pattern has become folliculopustular on this left shoulder, and the itch is manifested as early excoriations.

Figure 6.8 The typical folliculopapules over the right shoulder and clavicle are often ignored, or misdiagnosed as bacterial, leading to antibiotics that make matters worse.

Figure 6.9 Same patient as 6.8. The extension of the atopic dermatitis combined with the small folliculopapules from the neck and the forehead into the scalp, with no evidence of psoriatic scale, suggest the combination diagnosis. The failure of oral antibiotics and topical steroid scalp lotions and creams solidifies the case.

Figure 6.10 Distal onycholysis points toward psoriasis; itch and response to ketoconazole point to the inciting microbiological stimulus to trauma and Koebnerization.

Figure 6.11 Psoriasis descending the back of the neck, with folliculopapules and folliculopustules on the upper back.

Figure 6.12 Two questions must be asked at every visit: “What is in the pustules at this point?” And “What will be needed to get rid of them?”

Figure 6.13 Here, a microscopic slide “coverslip” is used to sample a pustule’s contents.

Figure 6.14 All from a single pustule, at various ages and stages. A small cap-shaped newborn larva is at top left.

Figure 6.15 The life cycle includes molting.

Figure 6.16 This little hair and its surrounding plug were the only foreign material in this pustule.

Chapter 08

Figure 8.1 The original liquid preparation in the mid-1970s was a challenge to tolerate, but alternatives were few.

Figure 8.2 These comedones developed in a 16-year-old while he was on a full anti-inflammatory dose of doxycycline as successful treatment for pityriasis lichenoides chronica.

Figure 8.3 This variety of fine closed comedonal acne with hundreds of lesions is a challenge, but proper use of topical retinoids will clear the tiny milia-like folliculopapules.

Figure 8.4 One of the earliest cases of a very upset bridesmaid whose waxing while on isotretinoin took off a strip of upper lip epidermis.

Figure 8.5 Her eyebrows also lost a layer—fortunately, the wedding was over a week away.

Figure 8.6 High-dose Accutane. Note the (pre-existing) facial scarring as well as the extensive cheilitis (chapped lips).

Figure 8.7 Same patient—a peeled heel.

Figure 8.8 There are only two or three active lesions in the hairline, but the little folliculopustules on the forehead are classic.

Figure 8.9 Often monomorphic folliculopapules, the lesions can be obvious folliculopustules and the surrounding urticarial erythema hints at the itch.

Figure 8.10 It is quite common to find all the diagnostic lesions with their tops scratched off.

Figure 8.11 The lady also had active forehead “rosacea” and about four pre-sternal folliculopustules.

Figure 8.12 First visit April—blepharitis noted but thought to be bacterial (note pustule—white arrow—medial to telangiectatic area) with a history of styes.

Figure 8.13 (A) In August, the cheeks were worse despite antibiotics. The forehead is also involved, but the left lower eyelid tells the tale. (B) The bacterial pustules were gone, but the telangiectatic eyelid area had become nodular. KOH from the nose pustule was positive for

Demodex

and was cleared with ivermectin.

Figure 8.14 The

Malassezia

yeast causes the itch, but the patient does the damage. This is the excoriated shawl syndrome.

Figure 8.15 Patients are often labeled neurotic or psychotic when the problem reaches this extent. The itch

can

drive them crazy.

Figure 8.16 Dutasteride 0.5 mg/day (A) started in March 2007, with minimal dietary restriction due to compliance problems; (B) at seven months, October 2007; (C) at 19 months, October 2008, with dietary compliance improving; and (D) at 22 months, January 2009.

Figure 8.17 Dutasteride 0.5 mg/day (A) started February 2007 with full dairy restriction. From the “tag,” the anus is at 11 o’clock and the sinus is at 1–3 o’clock. Note the firm oval swollen nodule at 1 o’clock in the whole complex. (B) At 17 months (July 2008), the nodule has resolved, and the sinus is more obvious at 3 o’clock as the swelling decreases. (C) At 29 months (July 2009), the original nodule has settled, the central tag has shrunk, the sinus has healed from below, and the patient is asymptomatic.

Figure 8.18 Total blockade requires both 5α-reductase inhibitors and avoidance of all dairy.

Figure 8.19 These comedones are “pouting” at the end of a third month on isotretinoin. The patient was distressed by the acuteness of the inflammation as each erupted and then left behind the brown post-inflammatory hyperpigmantation “scars.”

Figure 8.20 After 48 hours, these lesions will be almost imperceptible. All the tiny incisions were made transversely with a 30-gauge needle with no anesthesia, then gentle side pressure was used to pop out the contents using the smooth polished edge of an Unna comedo extractor. Bleeding is stopped with gentle pressure after hydrogen peroxide cleansing and a gentle alcohol wipe. Petroleum jelly or benzoyl peroxide gel is applied about an hour before bed.

Figure 8.21 Left to right: a semi-sharp spoon curette, a polished and rounded Unna-type perforated spoon comedo extractor, a 4-mm and a 7-mm disposable biopsy punch, and blunt-tipped scissors, SuperCut® curved 5.5-in. Mayo (Miltex, York, PA) or 02.11.10 curved blunt 10.5-cm (Medicon, Germany).

Figure 8.22 The patient was unable to make a timely appointment and took herself to the local emergency room, where the standard of care is incision and drainage (I&D). The healing stab wounds are closed over, and the underlying indurated tissue is palpably indurated and very tender.

Figure 8.23 These 6 mm biopsy punch excisions yielded pieces of residual follicular material. The ferric chloride and petrolatum are all that are needed postoperatively. Simple adhesive bandage over the petrolatum is all that is required until healing.

Figure 8.24 (A) Initial lesion thought to be innocent despite patient’s warning, (B) three weeks later, (C) scissors excision out to margins, (D) debridement complete using gauze grattage, (E) ferric chloride hemostasis, and (F) result at six months.

Figure 8.25 This sinus that ran from the 4 cm mid-buttock abscess to the anal verge was unroofed three weeks prior to the photo. The patient had used nothing on it but petrolatum while he continued his work as a coast-to-coast truck driver. When it healed, a second sinus from a second buttock lesion to the perineum and a third from the perineum to the scrotum were likewise unroofed without incident.

Figure 8.26 This is the closest I have seen to a “pure” sample of IPGM. Whether clear or cloudy, sterile or contaminated with bacteria, avascular or showing a pinkish glow, soft and easily removed with grattage or requiring a curette to separate from the base of the wound, the IPGM is the closest thing to a hallmark of acne inversa that has been described. It is unique in dermal pathology and warrants extensive investigation to delineate its source and functional capacities.

Figure 8.27a (A) The recurrence occurred within six months of the original surgery, despite intralesional steroids and antibiotics. It was unroofed successfully (B) The patient sought surgical care only when her perineal and peri-anal involvement became intolerable. There were only a few Dowling–Degos disease lesions in the axillae, and they were thought to be simple freckles until gluteal cleft biopsy confirmed the diagnosis.

Figure 8.27b Associated Dowling–Degos disease.

Figure 8.28 This association is not uncommon, suggesting that the tissue defect in follicular support may be responsible for more than just the weakness around the sebofollicular junction.

Figure 8.29 (A) Preoperative extent of lesions. (B) Post-excision to fat. (C) Split-thickness donor graft “meshed” to provide drainage, fresh cells, and coverage. (D) Mesh graft applied to wound and secured with staples. (E) Healing wounds showing partial “take” of grafts over pubis and repigmentation of healing donor site on thigh. (F) Final result at 1 year after healing of wounds and repigmentation of donor site.

Guide

Cover

Table of Contents

Begin Reading

Pages

iii

iv

ix

x

xi

xii

xiii

xiv

xv

xvi

xvii

xviii

xix

xx

xxi

xxii

xxiii

xxiv

xxv

xxvi

xxvii

xxviii

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

Acne

Causes and Practical Management

F. William Danby

Adjunct Assistant Professor of Surgery

Section of Dermatology

Geisel School of Medicine at Dartmouth

Hanover, New Hampshire,

USA

This edition first published 2015; © 2015 by John Wiley & Sons, Ltd.

Registered officeJohn Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK

Editorial offices9600 Garsington Road, Oxford, OX4 2DQ, UKThe Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK111 River Street, Hoboken, NJ 07030-5774, USA

For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell

The right of the author to be identified as the author of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.

Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought.

The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by health science practitioners for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom.

Library of Congress Cataloging-in-Publication Data

Danby, F. William, author. Acne : causes and practical management / F. William Danby.  p. ; cm. Includes bibliographical references and index.

 ISBN 978-1-118-23277-4 (cloth)I. Title. [DNLM: 1. Acne Vulgaris. 2. Hidradenitis Suppurativa. 3. Rosacea. WR 430] RL131 616.5′3–dc23

      2014032057

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Preface

This book came to be written for one very simple reason. Somebody suggested that Martin Sugden, my initial contact at Wiley, approach me to write it. While I had considered the possibility of a book—indeed, friends and colleagues had encouraged me to take the leap—the search for a publisher seemed daunting and life’s other commitments (plus a serious lifelong expertise in procrastination) ruled.

Martin’s invitation arrived at a time when, as the reader will see, there are very significant new thoughts and understandings arriving in the world of the acnes. Indeed, some have not reached the shores of North America, some have not yet been published, and some have just recently popped up as novel considerations. The field is moving fast enough that leaving something out is all but inevitable, and if you find I missed something you consider significant, please do let me know your thoughts. Now seems like a great time to start a file for a second edition.

All of this new material needs to be sifted and evaluated for logical consistency with the whole, and such reflection and consideration takes time. For me such time is usually stolen from the beginning of the day’s busy activities, in the shower. Indeed, it would not be too big a stretch to say that this present effort was written, or at least conceived and conceptualized and seriously mulled over, during about 40 years of morning showers.

Ultimately, this book is written for our patients. We commonly use the phrase “suffering from acne,” but usually without thinking how deeply the suffering goes.

As a teenager with bad skin, Janis Ian knew about that. She composed and sang “At Seventeen” in the early 1970s. Her poignant lyrics are a lesson in the impact of acne on self-image.

I learned the truth at seventeenThat love was meant for beauty queensAnd high school girls with clear skinned smilesWho married young and then retired.The valentines I never knew,The Friday night charades of youth,Were spent on one more beautiful.At seventeen I learned the truth…

And those of us with ravaged faces,Lacking in the social graces,Desperately remained at homeInventing lovers on the phoneWho called to say “come dance with me”And murmured vague obscenities.It isn’t all it seems at seventeen…

To those of us who knew the painOf valentines that never cameAnd those whose names were never calledWhen choosing sides for basketball.It was long ago and far away,the world was younger than todaywhen dreams were all they gave for freeto ugly duckling girls like me…

These lyrics have haunted me for decades while I’ve looked for explanations in the hope that the “ugly ducklings” of both sexes can eventually be spared the pains brought on by “the blight of youth.”

My initial interest in hormones, the fuel of the acnes, was “by exclusion” rather than by choice. As final-year dermatology residents in Toronto, we were each expected to write a review on a “basic science” topic. The only subject that was of any marginal interest to me and had not been dealt with by my senior residents was “Hormones and the Skin.” It has been a long road from 24-hour urine collections for ketogenic steroids, through the early days of dialyzable free testosterone, to the newly revealed mysteries of FoxO1 and mTORC1.

The original stimulus to look into diet as a cause of acne came from the first dermatologist in our family, my father. He had a case of a young dairy farmer whose well water was contaminated by agricultural bromides (see “The Farmer’s Boys,” Section 2.3.1). That original question got me wondering about diet as a cause of acne, partly because I was curious about the role of chocolate, and that led in due course to this book being written. I set up a semiquantitative patient questionnaire that included just about all common foods and drinks. I suspected the relationship between acne and milk after about two years of patient interviews done over 35 years ago. Osler’s admonition to “Listen to your patient, he is telling you the diagnosis” led not to the diagnosis but to a strong suspicion of the etiology of acne.

Already interested in “hormones in the skin,” I had been keeping an eye on the literature. I was unaware of the presence of hormones in milk until Janet Darling’s early 1970s papers came to my attention. “Chance favored the prepared mind,” and I found that a Pasadena dermatologist named Jerome Fisher had been studying acne, milk, and the steroid hormones he suspected in milk for years, since the early 1960s. A reference to his work appeared in Time magazine in 1966. I contacted him in 1979 and he sent me the carbon copies of his unpublished 1965 manuscript. Charles Bird at Queen’s Endocrinology did our first ‘free T’ assays. Thus, steroid hormones remained my prime suspects. By 2000 I felt that I was in a position to propose a formal study, so I asked for a meeting with Walter Willett, professor and head of the School of Nutrition at the Harvard School of Public Health.

That study was underway at Harvard in 2002 when Loren Cordain’s paper raised the question of the role of a low-glycemic-load (or Paleolithic) diet in preventing acne and other Western diseases. It had not occurred to the multinational team of which Cordain was a member that the absence of acne might have been due to the absence of dairy products. A phone call confirmed that the dairy intake of these tribes was indeed exceptionally low (in the New Guinea group) and absolute zero (in the Paraguay group). In late 2002 Clement Adebamowo, the Harvard group’s principal investigator, produced preliminary evidence of the epidemiological link between milk and acne in the Nurses Health Study data. In early 2005, the first of three papers demonstrating the significant association was published.

Meanwhile, another member of the Papua–Paraguay team returned to Australia and was involved in the design and conduct of several clinical studies that linked low-glycemic diets to clinical improvement of acne in a small number of young men. This reinforced the Australian thesis that the prime dietary mover of acne was the high glycemic load of the Western diet. Indeed, the most active collaborator, Robyn Smith, was awarded her PhD on the strength of that high-glycemic-load theory just a few short years after Clement Adebamowo earned his ScD based on the dairy and milk association with acne. Their contributions are reviewed in Appendix B.

Subsequently, Professor Bodo Melnik has presented us with what appear to be the pieces of the jigsaw puzzle that allow us to see almost the complete picture.

Understanding the complex relationships that form the background for these three diseases is essential in order to provide the “deliverable,” that is, a book on the acnes that will be, in Martin’s succinct description, “practical.” Within that word are several messages, including the need to write for a broad audience, from researcher to patient, and from busy dermatologists to patients’ parents. The researcher will need to forgive the helping hand of explanation that is occasionally extended to bring readers up to speed, and the beginner in the field will need to put up with (or look up) some unavoidable jargon. If and where I fail, always remember that Wikipedia is your friend, and deserves your support. While much of the book provides the necessary basic science to help with comprehension of the mechanisms discussed, this is not an academic text. Others are better at that than I. Nor will this be a catalog of every paper written on each and every aspect of these disorders, supplemented with my comments. It is instead my personal view, from the practical side, an overarching synthesis supported by selected references.

The first aim of this book is to provide practical guidance to managing the three acnes. There are several other books on acne that aim at being practical, so why is this book different? Simple. Because I believe that the longstanding concepts of the acnes’ cause and development, as still held by other authors are, in a word, outdated. That leads to the second aim of the book, to update the concepts upon which therapy must be based. The third and most important aim is to encourage prevention of the processes that lead to and perpetuate the acnes, ultimately making active, expensive, drug-based therapy unnecessary.

My intent is to provide the practical options, as I see them, for both patients and prescribers. At the same time I hope it will serve to nudge scholars and researchers in directions that remain both unexplored and promising.

It will also guide you to cost-effective therapy. I am not interested in marketing anything. I have no present financial interest in anything I am discussing, but if you look up the medical literature you will find that I was involved in paid clinical trials in the distant past. That means I may annoy some of my colleagues. My challenge will be to disagree without being disagreeable. Because this work describes three variants of a single disorder, there are shared features and shared pathogenic processes. This leads to unavoidable duplication. The alternative would be to lead the reader on a merry chase through a book filled with links to other chapters and sections. I have kept these internal references to a minimum, providing a cohesive self-contained unit dealing with each of the acnes.

Continuing medical education (CME) standards in the United States require notification of audiences if any drug is used “off label,” meaning that it has not been specifically studied to US Food and Drug Administration (FDA) standards for the particular disorder being discussed. Most of the medications used in dermatology are regularly used off label. I will not bore the reader and use valuable space to repeat this caveat throughout the book. Almost this entire book is in my own words but where others’ words serve better than I can paraphrase them, I will quote them with attribution. As the sole author, any mistakes are mine and I do appreciate constructive criticism.

Thanks go first to Lynne Margesson. She “came on service” as my junior resident and is my spouse of 39 years, my practice partner, and mother of our two children. She did not hesitate at all in giving me the green light for this project, even though she had a pretty good idea what it would entail. I would love to thank my mentors, if I had any, but I do owe debts of gratitude instead to the several researchers, teachers, writers, and, most importantly, thinkers who have contributed to the field. Howard Donsky nudged his residents to look at the basic sciences in depth. My father, Charles Danby, was a dermatological innovator in his own right. Janet Darling did the initial determinations of the levels of steroid hormones in milk. Sir Kenneth Charles Calman detailed the existence of the first intracrine enzymes in the follicular keratinocytes. The late Jerome Fisher’s study of milk and acne and suspicion of hormones helped me down this road. Loren Cordain’s studies of aboriginal diets inadvertently set the baseline of “no milk, no acne.” Peter Pochi shared a confidence. Walter Willett had the courtesy to listen and then facilitate a fresh look at the Nurses Health Study II and other data. I owe special thanks to Clement Adebamowo for doing all the heavy lifting for that work. Dawn Danby and Paul Waggoner provided the line drawings of the ‘FPSU.’

In the acne inversa/hidradenitis suppurativa (AI/HS) area, thanks are due to Michelle Barlow for lighting a fire under us, to Gregor Jemec for support and ongoing collaboration, to Christos Zouboulis for opening doors, to Stuart Maddin for encouraging me to “focus” (always a challenge) and for encouraging me to contact Professor Zouboulis, to Maximilian von Leffert and Prof. Wolfgang Marsch for collaborating on the “follicular support” project, and to Robert Bibb for being the first to try a dairy-free diet in AI/HS. Special thanks go to numerous patients willing to try novel therapies, some out of acquiescence to my requests, some out of curiosity, and many out of the desperation and frustration that often accompany AI/HS.

This book presents an overview of the way I believe the acnes begin and how they progress through their various stages. It also provides personal glimpses into areas not yet fully explored. I will offer new hypotheses, consider areas of controversy, and touch on other hormonally related disorders that need further investigation.

The acnes exist in a four-dimensional spectrum, changing with time. They share a common cause but are unique in their individual three-dimensional presentations. My hope is to persuade you to see the acnes as I see them, and to learn to prevent them. Where others have failed at prevention, I hope to provide you with a few new and original treatment approaches.

Bill Danby

Hopkinton, New Hampshire

Practical acne therapy

There is a common theme in the three acnes. Pores are blocked; they burst, get inflamed, scar down, and heal. Whether the patient (you, perhaps?) experiences acne vulgaris, acne rosacea, or acne inversa/hidradenitis suppurativa (AI/HS) depends upon variables that include lesion location, patient’s age, gender, family history, diet, sun exposure, and several others.

So let’s start at the beginning.

With a look in the mirror.

How bad is it?

Staging and grading acne are essential in research but of little practical value in individual cases.

If you’ve got it, you’ve got it. Measuring it doesn’t make it better.

Acne vulgaris that is “the end of my life forever” for one teen can be ignored by another.

Acne rosacea can be embarrassing beyond belief and a huge social handicap, or a minor nuisance.

Acne inversa can be an occasion “boil” every few months, or it can be life-destroying.

Be practical

: If you’ve got it, and you want it gone, take the practical approach.

Genetics

If you inherited the genes for any acne, like 90% of us, that’s unfortunate. Nothing fixes genes.

Be practical

: You might want to choose a mate someday with

their

genes in mind if you want to look out for your children’s risk of acne.

Diet

We know acne is caused by the male hormone dihydrotestosterone (DHT).

DHT works by linking to a male hormone (androgen) receptor.

It is like putting a key in the keyhole to open a door.

The androgen receptor (keyhole) needs to be open to accept the key.

Opening the keyhole requires insulin and/or insulin-like growth factor 1 (IGF-1).

Milk and milk products raise both insulin and IGF-1, opening the androgen receptor.

Sugar also raises insulin levels, helping even more to open the androgen receptor.

Foods that turn into sugar quickly (high-glycemic-index foods) also raise insulin levels.

Milk and milk products also actually contain androgens (the keys to the keyhole).

Milk and milk products also actually contain other hormones that turn into androgens.

So both dairy and sugary foods can open the androgen receptor.

But dairy also supplies the androgens to turn on acne. Dairy is triple trouble.

Be practical

:

Change to a truly natural diet.

Eliminate all dairy.

Go “low glycemic load.”

Hormones

Hormones cause acne.

No hormones = no acne.

Eliminating hormones in either sex is not practical.