14 - 80 - ACNE VARIANTS AND ACNEIFORM ERUPTIONS

Question 1

Answer 1

Infantile acne presents at 3 to 6 months of age classically with open and closed comedones over the cheeks and chin. (Fig. 80-2). Papules, pustules, and nodules can also present on the face. Pitted scarring may occur even with relatively mild disease. Infantile acne is caused in part by the transient elevation of dehydroepiandrosterone (DHEA) produced by the immature adrenal gland. 4 Additionally, during the first 6 to 12 months of life, boys may also have an increased level of luteinizing hormone (LH) that stimulates testosterone production. Around 1 year of age, these hormone levels begin to stabilize until they surge again during adrenarche. As a result, infantile acne usually resolves around 1 to 2 years of age. Treatment generally consists of topical retinoids and benzoyl peroxide. Oral therapy with erythromycin, azithromycin, trimethoprim, or isotretinoin can be used in severe or refractory cases.

Question 2

most severe form of acne and may occur with or without systemic symptoms

Answer 2

Acne fulminans (also known as acute febrile ulcerative acne)

The sudden appearance of inflammatory, tender, oozing, friable plaques with hemorrhagic crusts characterizes this extreme presentation. The lesions predominate on the chest and back (Fig. 80-3) and rapidly become ulcerative and heal with scarring. The disease is reported to occur primarily in teenage boys. Systemic symptoms are often present. The patients are febrile; have a leukocytosis of 10,000 to 30,000/mm 3 white blood cells; and usually have polyarthralgia, myalgia, hepatosplenomegaly, and anemia. Bone pain is common, especially at the clavicle and sternum. Radiologic examination may demonstrate lytic bone lesions. Occasionally, there is accompanying erythema nodosum. Although this disease is often classified with acne conglobata, there are basic differences. The onset of acne fulminans is more explosive; nodules and polymorphous comedones are less common; the face is not involved as frequently, and the neck is usually spared; ulcerative and crusted lesions are unique; and systemic symptoms are more common.

Systemic glucocorticoid therapy, along with intralesional glucocorticoids, is first-line treatment for acne fulminans. Systemic glucocorticoids (prednisone 0.5–1.0 mg/kg/day) are started before isotretinoin for 2 to 4 weeks, depending on the severity of systemic symptoms, and continued during the first few weeks to months of isotretinoin therapy. The initial dosing of isotretinoin should be quite low (0.1 mg/kg/day) during the initial weeks of therapy until the inflammation is controlled. 6 The daily dose of glucocorticoids should be slowly decreased as tolerated over weeks to months. Alternately, 0.5 mg/kg/day of isotretinoin started immediately with 10 mg of prednisolone three times daily has been recommended. 7 Dapsone in conjunction with isotretinoin has been reportedly beneficial in the treatment of acne fulminans associated with erythema nodosum. 8 Cyclosporine, anakinra, and tumor necrosis factor (TNF) inhibitors have also been used in difficult cases of acne fulminans.9-11

Question 3

What is SAPHO SYNDROME

Answer 3

SAPHO syndrome is manifested by synovitis, acne, pustulosis, hyperostosis, and osteitis. It is predominantly associated with hyperostosis of the anterior chest, palmoplantar pustulosis, hidradenitis suppurativa, and acne fulminans. Its cause is unknown. Reported successful treatments for SAPHO syndrome include nonsteroidal antiinflammatory drugs, sulfasalazine, infliximab, adalimumab, methotrexate. 12 Paradoxically, worsening of SAPHO skin manifestations can be seen with anti-TNF agents. 13,14 The bisphosphonates are beneficial for treating the associated bone pain.

Question 4

What are PAPA, PASH, AND PAPSH SYNDROME

Answer 4

PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), PASH (pyoderma gangrenosum, acne and hidradenitis suppurativa) and PAPASH (pyogenic arthritis, acne, pyoderma gangrenosum and hidradenitis suppurativa) are a group of systemic autoinflammatory disorders resulting from dysregulation of the innate immune system and over production of interleukin (IL)-1. 16 Patients with these disorders have a variable combination of sterile neutrophilic skin lesions, including acne, pyogenic granuloma, and hidradenitis suppurativa, and pyogenic arthritis. They may also give a history of inflammatory bowel disease and pancytopenia after administration of sulfacontaining medications. Mutations in the protein serinethreonine phosphatase interacting protein (PSTPIP1) results in an increase in IL-1β production. 17 There have been reports of successful treatment with cyclosporine, dapsone, infliximab, and anakinra.18,19

Question 5

an autosomal dominant disorder marked by synostoses of the cranium, vertebral bodies and hands and feet

Answer 5

Apert syndrome, also known as acrocephalosyndactyly

It is caused by a mutation in the gene encoding FGFR-2. These patients have a diffuse acneiform eruption that often involves the arms, buttocks, and thighs. It is typically very resistant to treatment, but excellent responses to isotretinoin have been reported. 55 Patients with Apert syndrome may also present with severe seborrhea, nail dystrophy, and cutaneous and ocular hypopigmentation.

Question 6

Answer 6

The facial Afro-Caribbean eruption (FACE) is another variant of periorificial dermatitis characterized by uniform, granulomatous sarcoidal papules distributed over the typical periorificial areas. 60 (Fig. 80-6) Distinguishing features include involvement of the upper eyelids and helices of the ears. 61 Histology is similar to granulomatous perioral dermatitis.

Question 7

neonatal acne occurs around what age?

It resolves spontaneously within how many months?

Answer 7

2 weeks of age and resolve spontaneously within 3 months

Question 8

Infantile acne is caused in part by the transient elevation of what hormone ?

Answer 8

**dehydroepiandrosterone (DHEA) **produced by the immature adrenal gland

Question 8

Infantile acne presents at what month?

Answer 8

3 to 6 months

Question 9

Mid-childhood acne is defined as appearing between what ages?

Answer 9

1 and 7 years of age

any child with acne in mid-childhood should be evaluated for other signs of hyperandrogenism (pubic or axillary hair, testicular enlargement or breast development)

Question 10

mixture of comedones, papules, pustules, nodules, abscesses, and scars arising in a more generalized pattern over the back, buttocks, chest, and, to a lesser extent, on the abdomen, shoulders, neck, face, upper arms, and thighs

Answer 10

Acne conglobata

Draining lesions discharge a foul-smelling serous, purulent, or mucoid material.

Subcutaneous dissection with the formation of multichanneled sinus tracts is common

Question 11

management of acne conglobata

Answer 11

• The use of isotretinoin is highly effective in these patients.
• However, because severe flares may occur when isotretinoin is started, the initial dose should be 0.5 mg/kg/day or less, and systemic glucocorticoids are often required either before initiating isotretinoin therapy or as concomitant therapy.
• Systemic tetracyclines, intralesional glucocorticoids, systemic glucocorticoids, surgical debridement, surgical incision, and surgical excision may also be required to effectively control acne conglobata

Question 12

most severe form of acne and may occur with or without systemic symptoms

Answer 12

Acne fulminans (also known as acute febrile ulcerative acne)

Question 13

The sudden appearance of inflammatory, tender, oozing, friable plaques with hemorrhagic crusts characterizes this extreme presentation.

Answer 13

Acne fulminans (also known as acute febrile ulcerative acne)

• The lesions predominate on the chest and back and rapidly become ulcerative and heal with scarring.
• The disease is reported to occur primarily in teenage boys

Question 14

symptoms associated with acne fulminans

Answer 14

• The patients are febrile;
• have a leukocytosis of 10,000 to 30,000/mm3 white blood cells; and
• usually have polyarthralgia, myalgia, hepatosplenomegaly, and anemia.
• Bone pain is common, especially at the clavicle and sternum.
• Radiologic examination may demonstrate **lytic bone lesions. **
• Occasionally, there is accompanying erythema nodosum.

Question 15

difference of acne fulminans and acne conglobata

Answer 15

• The onset of acne fulminans is more explosive;
• nodules and polymorphous comedones are less common;
• the face is not involved as frequently, and
• the neck is usually spared;
• **ulcerative and crusted **lesions are unique; and
• systemic symptoms are more common

Question 16

first-line treatment for acne fulminans

Answer 16

Systemic glucocorticoid therapy, along with intralesional glucocorticoids

• Systemic glucocorticoids **(prednisone 0.5–1.0 mg/kg/day) **are started before isotretinoin for 2 to 4 weeks, depending on the severity of systemic symptoms, and continued during the first few weeks to months of isotretinoin therapy
• The i**nitial dosing of isotretinoin **should be quite low **(0.1 mg/kg/day) **during the **initial weeks of therapy **until the inflammation is controlled
• The daily dose of glucocorticoids should be** slowly decreased as tolerated over weeks to months. **
• Alternately, 0.5 mg/kg/day of isotretinoin started immediately with 10 mg of prednisolone three times daily has been recommended
• Cyclosporine, anakinra, and tumor necrosis factor (TNF) inhibitors have also been used in difficult cases of acne fulminans

Question 16

has been reportedly beneficial in the treatment of acne fulminans associated with erythema nodosum

Answer 16

Dapsone in conjunction with isotretinoin

Question 17

An explosive flare of tender, oozing, friable plaques with hemorrhagic crusts occurs with or without associated systemic symptoms after initiation of isotretinoin therapy

Answer 17

ISOTRETINOIN-INDUCED ACNE FULMINANS

• The flaring typically arises within the first month of treatment but may occur later.
• Patients with severe inflammatory acne in particular are at risk

Question 18

how can you prevent flaring of acne when initiating isotretinoin?

Answer 18

• Lower starting doses of **isotretinoin (0.3 to 0.5 mg/kg/day) **and the concomitant addition of systemic corticosteroids may prevent flaring.
• If isotretinoin-induced acne fulminans does occur, the isotretinoin dose should be lowered or discontinued and prednisone therapy immediately started, following the guidelines for the management of acne fulminans above.

Question 19

SAPHO syndrome

Answer 19

synovitis, acne, pustulosis, hyperostosis, and osteitis

It is predominantly associated with hyperostosis of the anterior chest, palmoplantar pustulosis, hidradenitis suppurativa, and acne fulminans.

Question 20

Reported successful treatments for SAPHO syndrome

Answer 20

nonsteroidal antiinflammatory drugs, sulfasalazine, infliximab, adalimumab, methotrexate

Question 21

Paradoxically, worsening of SAPHO skin manifestations can be seen with what agents

Answer 21

anti-TNF agents

Question 22

beneficial for treating the associated bone pain in SAPHO syndrome

Answer 22

bisphosphonates

Question 23

PAPA syndrome

Answer 23

pyogenic arthritis, pyoderma gangrenosum and acne

Question 24

PASH syndrome

Answer 24

pyoderma gangrenosum, acne and hidradenitis suppurativa

Question 25

PAPASH syndrome

Answer 25

pyogenic arthritis, acne, pyoderma gangrenosum and hidradenitis suppurativa

Question 26

PAPA, PASH and PAPASH syndrome are a group of systemic autoinflammatory disorders resulting from dysregulation of the innate immune system and over production of what IL?

Answer 26

IL-1

Question 27

what mutation results in an increase in IL-1β production?

Answer 27

protein serinethreonine phosphatase interacting protein (PSTPIP1)

Question 28

Often quite mild acne is systematically and neurotically excoriated, leaving crusted erosions that may scar.

Answer 28

Acne excoriée (or acne excoriée des jeunes filles) ## Footnote They are categorized under obsessive-compulsive disorders and as such should be comanaged with psychiatry to address both the acne and the underlying psychogenic excoriation.

Question 29

Acneiform eruptions have been observed after repetitive physical trauma to the skin such as pressure, friction, or rubbing

Answer 29

ACNE MECHANICA ## Footnote * Two types of reactions result, either a flare in acne with **comedones and inflammatory papules (“acne mechanica”)** or **follicular inflammatory lesions (“folliculitis mechanica”)** * can occur from clothing (belts and straps), sports equipment (football helmets and shoulder pads), and with crutches and prosthetics * classic example of acne mechanica is **“fiddler’s neck,” **produced where the violin pad repetitively rubs against the player’s lateral neck * Alterations in the barrier function, microbiome, and activation of innate immune system, as well as keratinocyte disruption and increase in IL-1a are purposed to play a role

Question 30

rare and disfiguring variant of acne vulgaris is acne with solid facial edema

Answer 30

Morbihan disease ## Footnote * There is a** woody edema** of the mid third face with accompanying **erythema and acne** * Treatment with low dose i**sotretinoin (0.2–0.5 mg/kg/day) alone** **or in combination with oral glucocorticoids, ketotifen (1–2 mg/day), or clofazimine for 4 to 5 months** has been reported to be beneficial

Question 31

clinical markers of PCOS

Answer 31

Hyperandrogenism, acne, insulin resistance, and acanthosis nigricans ## Footnote * PCOS should be suspected in women with any combination of **oligomenorrhea, clinical or biochemical hyperandrogenism, or polycystic ovaries on ultrasound scan** * Women with PCOS are at increased risk of infertility, impaired glucose tolerance, type 2 diabetes, dyslipidemia, endometrial cancer, and cardiovascular disease

Question 32

Premenarchal women with acne and hirsutism should be screened for PCOS with what lab test?

Answer 32

serum free testosterone level

Question 33

treatment of PCOS

Answer 33

* Combined **oral contraceptives with spironolactone** can be helpful in controlling acne and hirsutism * The addition of **metformin** can also beneficial * Additional treatment consists of **weight management, lipid control, regulation of insulin resistance, and fertility assistance**

Question 34

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by varying defects in what enzyme?

Answer 34

**21β-hydroxylase**

Question 35

what lab test can be requested to investigate for presence of Congenital adrenal hyperplasia (CAH)?

Answer 35

dehydroepiandrosterone sulfate (DHEAS) in the range of 4000 to 8000 ng/mL

Question 36

manifestations of CAH

Answer 36

* Neonates are screened at birth for the classic type and typically present with ambiguous genitalia and salt wasting * The nonclassic type is not identified at birth and can present throughout childhood and adolescence * Patients with this type of CAH have normal cortisol levels but **increased androgens** * Female patients present with findings similar to PCOS, including **precocious puberty, irregular menses, polycystic ovaries, hirsutism, and acne.** * Findings of CAH in males are often subtle and acne may be the only sign. * CAH should be considered in patients who do not respond to treatment * Treatment of patients with CAH consists of** low-dose replacement of glucocorticoids, as well as oral contraceptives, spironolactone, or flutamide in females.**

Question 37

as early as how many weeks can steroid folliculitis occur after initiation of systemic steroids ?

Answer 37

2 weeks ## Footnote Similar lesions may follow the prolonged application of topical glucocorticoids to the face or with inhaled steroids for asthma

Question 38

differentiate lesions of steroid folliculitis from acne vulgaris

Answer 38

* The lesions, which are usually all in the **same stage of development,** consist of **small pustules and red papules** * In contrast to acne vulgaris, they appear mainly on the **trunk, shoulders, and upper arms,** with lesser involvement of the face. * comedones, cysts, and scarring are unusual * Treatment consists primarily of **stopping any corticosteroid use. ** * Typical acne treatments such as **topical retinoids and antibiotics** may also be helpful

Question 39

other drugs that can cause a monomorphic, diffuse papular eruption that mimics steroid folliculitis (Drug-induced acneiform eruptions)

Answer 39

BEG PHIL Halo * BRAF inhibitors * Epidermal growth factor receptor inhibitors (cetuximab, panitumumab, necitumumab, pertuzumab, and small-molecule tyrosine kinase inhibitors gefitinib, erlotinib, afatinib, osimertinib, and lapatinib) * Glucocorticoids * Phenytoin * High-dose vitamin B complex * Isoniazid * Lithium * Halogenated compounds (containing iodides/ bromides - often found in cold and asthma remedies, sedatives, radiopaque contrast material, kelp, and other vitamin and mineral combinations)

Question 40

frequent side effect of the EGFR inhibitors

Answer 40

perifollicular, papulopustular eruption distributed on the face and upper torso ## Footnote * For mild disease, t**opical hydrocortisone 2.5% cream or clindamycin 1% lotion **is suggested. * For more severe disease, **higher strength topical steroids, doxycycline or minocycline, or low-dose isotretinoin **is recommended

Question 40

term that is used to describe occupational acne caused from chlorinated hydrocarbons

Answer 40

Chloracne ## Footnote * Chloracne classically affects the malar, retroauricular, and mandibular regions of the head and neck, as well as the axillae and scrotum * Most chloracne lesions clear up within 2 years, providing exposure to the chemical has stopped. * Treatment with topical or systemic retinoids or oral antibiotics may be beneficial

Question 41

most common cause of industrial acne

Answer 41

Cutting oils

Question 42

may occur in patients with preexisting acne vulgaris treated with long-term oral antibiotics, especially the tetracyclines

Answer 42

Gram-negative folliculitis ## Footnote * Gram-negative folliculitis may appear as either papulopustules concentrated around the nose or as deep-seated nodules. * Culture of these lesions may reveal **Enterobacter, Klebsiella, or Escherichia **spp. in the papulopustules or **Proteus** spp. in the nodules.

Question 43

Patients usually give a history of initial success with oral tetracyclines followed by a worsening of their acne

Answer 43

Gram-negative folliculitis ## Footnote * An appropriate antimicrobial agent with adequate gram-negative coverage should be used. * In recalcitrant cases, gram-negative folliculitis improves with **oral isotretinoin for 4 to 5 months.** * Gram-negative bacteria require a **moist environment for survival**, and the drying action of isotretinoin will kill the bacteria.

Question 44

this type of acneiform reaction may produce a yellow, atrophic plaque studded with large open comedones known as **Favre-Racouchot syndrome**

Answer 44

Radiation Acne ## Footnote * The lesions are usually symmetrically distributed on the temporal and periorbital areas. * The exact pathogenesis of Favre-Racouchot syndrome is unknown, but it is suggested that extensive UV exposure as well as exposure to harsh climates and smoking may be risk factors. * It can be treated with oral or topical retinoids as well as comedone extraction or CO 2laser

Question 45

In extreme heat, a severe acneiform folliculitis may develop. This is known as

Answer 45

TROPICAL ACNE ## Footnote * occurs mainly on the trunk and buttocks * It has many deep, large, inflammatory nodules with multiple draining areas, resembling acne conglobata

Question 46

This monomorphous eruption consists of multiple, uniform, red, papular lesions seen **after sun exposure.**

Answer 46

ACNE AESTIVALIS ## Footnote * It was initially called **Mallorca acne** * The eruption is caused by the effects of UV radiation, primarily **UVA** * Like polymorphous light eruption, patients with acne aestivalis **will flare on reexposure to UV light.**

Question 47

Preadolescent patients develop c**omedones, milia, and acneiform red papules **within the **nasal crease**

Answer 47

PSEUDOACNE OF THE NASAL CREASE ## Footnote * It can be familial or associated with the “allergic salute.”

Question 48

**autosomal dominant disorder** marked by **synostoses of the cranium, vertebral bodies and hands and feet**

Answer 48

Apert syndrome, also known as acrocephalosyndactyly,

Question 49

Apert syndrome, also known as acrocephalosyndactyly is caused by what mutation? ## Footnote * These patients have a diffuse acneiform eruption that often involves the arms, buttocks, and thighs. * may also present with severe seborrhea, nail dystrophy, and cutaneous and ocular hypopigmentation

Answer 49

mutation in the gene encoding** FGFR-2**

Question 50

Small inflammatory papules and pustules group around the mouth in a typically well demarcated pattern, with **sparing of the lip margin**

Answer 50

PERIORAL DERMATITIS/ PERIORIFICIAL DERMATITIS ## Footnote * acneiform eruption that occurs in a bimodal distribution **young children and young adults. ** * there is **female** predominance, mostly in adolescents and adults * If the **nose, eyes, or groin** region is involved, it is called **periforificial** dermatitis * The **neck, trunk, and extremities** are rarely involved but have been reported in children with the disorder. * Usually perioral dermatitis is **asymptomatic** with **occasional itchy or burning noted.**

Question 51

**larger, granulomatous inflammatory papules** coalesce into a well delineated plaque around the mouth with more likely involvement of the **periocular, perinasal, and groin areas**

Answer 51

periorificial granulomatous dermatitis

Question 52

known triggers for periorificial dermatitis

Answer 52

* topical or inhaled **corticosteroid** use, particularly fluorinated steroids and fluoride in dentifrices * Additionally, **demodex** may play a role in some cases of periorificial dermatitis

Question 53

treatment of periorificial dermatitis

Answer 53

* **Topical corticosteroid **use should be **avoided** because it tends to perpetuate the eruption. * In mild cases resulting from corticosteroid use, **discontinuation** of steroid application can alone be effective. * Alternate therapies include topical antimicrobial and antiinflammatory agents, including **metronidazole cream or gel, clindamycin gel or lotion, erythromycin gel, azelaic acid cream, and sodium sulfacetamide lotion**. * Topical **pimecrolimus** cream or **tacrolimus** ointment has also been used in to treat periorificial dermatitis and to diminish flares from topical steroid withdrawal. * In children,** oral erythromycin or azithromycin** may be added for refractory or severe cases, but **tetracyclines** are commonly used in adolescents and adults. * Recently, the antiparasitic agents **praziquantel** and **ivermectin** (both topical and oral) have been successfully used.