acne fulminans explosive systemic form of acne

REVIEW ARTICLE

Acne fulminans: explosive systemic form of acne

R Zaba,†,* RA Schwartz,‡ S Jarmuda,† M Czarnecka–Operacz,† W Silny†

†Department of Dermatology, Poznan University School of Medical Sciences, Poznan, Poland‡Dermatology, Pediatrics, Medicine, and Preventive Medicine and Community Health, New Jersey Medical School, Newark, NJ, USA

*Correspondence: R Zaba. E-mail: [email protected]

AbstractAcne fulminans (AF) is a rare severe form of acne vulgaris associated with systemic symptoms. It primarily affects

male adolescents. Although the aetiology of AF remains unknown, many theories have been advanced to explain it.

There have been reported associations with increased androgens, autoimmune complex disease and genetic pre-

disposition. The disease is destructive, with the acute onset of painful, ulcerative nodules on the face, chest and

back. The associated systemic manifestations such as fever, weight loss and musculoskeletal pain are usually

present at the onset. The patients are febrile, with leucocytosis and an increased erythrocyte sedimentation rate.

They may require several weeks of hospitalization. The treatment of AF has been challenging; the response to

traditional acne therapies is poor. The recommended treatment is aggressive and consists of a combination of oral

steroids and isotretinoin. To avoid the relapses, duration of such treatment should not be less than 3–5 months.

Although the prognosis for patients treated appropriately is good, these acute inflammatory nodules often heal with

residual scarring.

Received: 15 February 2010; Accepted: 26 August 2010

Keywordsacne fulminans, acne maligna, acne with polyarthritis, acute febrile ulcerative conglobata, isotretinoin, prednisolone

Conflicts of interestNone declared.

IntroductionAcne fulminans (AF), also known as acne maligna, is a severe,

ulcerative form of acne with an acute onset and systemic symp-

toms. This serious disease is rare and primarily affects Caucasian

male adolescents, aged 13–16 years, although it may also occur in

women.1,2 Its frequency is much lower in people of East Asian des-

cent, such as in Japanese, who tend to have a milder course than

in people of Northern European lineage. AF was originally

described in 1959 as acne conglobata with septicaemia by Burns

and Colville3, who described a 16-year-old student with acute feb-

rile disease and acne conglobata. In 1971, Kelly and Burns4 intro-

duced a term ‘acute febrile ulcerative conglobate acne with

polyarthralgia’ to name a syndrome with following features:

(i) sudden onset; (ii) severe ulceration without cyst formation;

(iii) fever and polyarthralgia; (iv) failure to respond to usual anti-

biotic therapy; and (v) good response to debridement in combina-

tion with steroid therapy. In 1975, Plewig and Kligman5 separated

this disease from acne conglobata and coined a term AF, which

emphasized the characteristic sudden onset and severity of the

illness. In 1977, Goldschmidt et al.6 reviewed thirteen cases of AF

and also reported eight cases of their own. They defined AF as a

rare disorder of male teenagers characterized by sudden appear-

ance of highly inflammatory, tender nodules on the back, chest

and face associated with various systemic signs. Since these reports,

approximately 100 patients with AF have been described.7

The primary clinical manifestations of this disease include

development of highly inflammatory and haemorrhagic, tender,

crusted nodules of the face, upper chest and back.8 Systemic symp-

toms, such as fever, chills, weakness and musculoskeletal pain,

tends to be evident at the onset. Less frequently, patients with AF

develop erythema nodosum, aseptic bone osteolysis, hepatospleno-

megaly or myositis.9,10 Patients typically have mild acne vulgaris

for about a year before the onset of their acute symptoms

(Table 1). AF can be the dermatological manifestation of the

SAPHO syndrome. The SAPHO (synovitis, acne, pustulosis,

hyperostosis and osteitis) syndrome was first described in 1987

and has been predominately associated with hyperostosis of the

anterior chest and various skin abnormalities such as palmoplantar

pustulosis, psoriasis, hidradenitis suppurativa, acne conglobata

and acne fulminans.11 AF has been reported to develop at the

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JEADV 2011, 25, 501–507 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology

DOI: 10.1111/j.1468-3083.2010.03855.x JEADV

onset of Crohn’s disease, but the significance of this association is

unclear.12

PathophysiologyThe aetiology of AF remains unknown, but infection, genetic

and immunological causes have been proposed. Many theories

have been advanced. One postulates that development of AF is

related to an explosive immunologically mediated type III

and ⁄ or type IV hypersensitivity reaction to Propionibacterium

acnes antigens.13 The massive contact of the immune system

with P. acnes antigens and ⁄ or P. acnes chemoattractants may

occur after isotretinoin-induced fragility of the pilosebaceous

duct epithelium. Another theory is that genetically determined

change in neutrophil activity – hyperreactivity to chemoattrac-

tants may result in decreased phagocytosis of P. acnes. Propioni-

bacterium acnes destruction is thought to result in mediator

release, including neutrophil chemotaxis, which may be responsi-

ble for the early flares seen on treatment with isotretinoin.

Patients developing severe flares of disease may be showing an

exaggeration of this response.14 Isotretinoin has been suspected,

as it may precipitate acne fulminans. In some patients, mild

cystic acne rapidly becomes ulcerative and necrotic acne with

systemic symptoms. AF may commence during isotretinoin,

tetracycline or erythromycin therapy.2 In these patients, the iso-

tretinoin dose was 0.5–1 mg ⁄ kg ⁄ day, that is, 40– 80 mg ⁄ day,

and the duration of treatment before AF origin averaged 3 weeks

(range, 1–7 weeks). Paradoxically, AF maybe treated successfully

with isotretinoin or with isotretinoin combined with systemic

steroids or other anti-inflammatory agents. Retinoids are known

to increase skin fragility through a reduction in number of tono-

filaments and desmosomal attachments with secondary accumu-

lation of epidermal amorphous material. Moreover, isotretinoin

could also act by inhibiting collagenase and gelatinase activity in

stimulated fibroblasts in vitro. Isotretinoin induces fragility of the

pilosebaceous duct epithelium and allows massive contact of

P. acnes antigens and ⁄ or P. acnes chemoattractants with the

immune system to occur. Interestingly, two siblings were

described, one with isotretinoin-induced eruptive pyogenic

granulomas (PG) in the course of severe acne, and the other

who developed isotretinoin-induced acne fulminans.15

Elevated blood levels of testosterone may play an important role

in the pathogenesis of acne fulminans.16 Three patients were

observed with AF possibly induced by high doses of testosterone

administrated for the treatment of excessively tall stature.17

Another example was a 21-year-old bodybuilder who developed

AF as a side-effect after 4 weeks of self-medication with high doses

of testosterone and anabolic steroids, taken to increase the mass of

his muscles.18 Despite testosterone intake, his serum testosterone

levels were found to be within normal limits. Testosterone levels

increase physiologically during puberty and may explain why this

disease primarily affects male adolescents. Large doses of andro-

genic or ⁄ and anabolic steroids increase the sebum excretion rate

in postpubertal men. Together with this increased sebum excretion

rate, there is an increased population density of P. acnes. The

increased amount of P. acnes or related antigen might, after reach-

ing a certain level, precipitate an immunological reaction in some

patients that leads to an outbreak of AF. The trigger for acne

induction seemed to be testosterone therapy in a patient with

Marfan syndrome.19 Acne may be the only clinical sign of andro-

gen excess in men. Placzek, Degitz, Schmidt and Plewig20

described a 15-year-old boy with 3-month history of deteriorating

acne, who suddenly developed fever, leucocytosis, an elevated

erythrocyte sedimentation rate and arthralgias. In this case, AF

was caused by androgen excess attributed to late-onset congenital

adrenal hyperplasia.

Another theory postulates that AF may be an autoimmune

complex disease. It has been postulated that an arthus reaction

was taking place when AF is seen with erythema nodosum, but no

circulating immune complexes were detected.9 Employing the

platelet aggregation test, a reliable method for detecting soluble

IgG complexes, circulating immune complexes may be docu-

mented in some with AF.21 Factors in favour of an autoimmune

aetiology of AF are the rapid response of the patient to systemic

steroids, the increase in gamma globulins and the decrease in C3

complement levels in several patients. Immune complexes are

found predominately in patients with musculoskeletal complaints.

Table 1 The main features of AF

Gender Male gender dominant

Age 13–22 years

Pathogenesis Unclear

Onset Acute and sudden

Localization Upper chest and back, shoulders, face

Clinical picture Ulcerative lesions covered with haemorrhagical crusts

Systemic signs Malaise, fever, fatigue, weight loss, arthralgias and myalgias, osteolytic bonelesions, splenomegaly, hepatomegaly

Laboratory findings Leucocytosis, increased ESR, anaemia, proteinuria, microscopical haematuria

Response to conventional antibiotic therapy Poor

Treatment of choice Systemic corticosteroids combined with isotretinoin

AF, acne fulminans; ESR, erythrocyte sedimentation rate.

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502 Zaba et al.

Although the pathogenesis of AF remains unknown, the associa-

tion with SAPHO syndrome suggests that systemic inflammatory

cytokinaemia, including tumour necrosis factor-a (TNF-a), might

be responsible. This is strengthened by the finding that the anti-

TNF-a agent, infliximab, shows beneficial effects on AF.22

Infectious factors have been considered to be important in acne

fulminans. An association of viral infection with AF has been sug-

gested by the onset of clinical symptoms 2 weeks after a measles

infection, implying that the measles can trigger a transient release

of inflammatory cytokines, resulting in AF in predisposed individ-

uals.23

Genetic and hereditary factors may play an important role in

some patients. AF has been reported in identical monozygotic

twins.24,25 In each case the age of presentation and severity of the

disease was similar. A hereditary nature has been suggested by the

identical age of presentation, the similar clinical picture and iden-

tical human leucocyte antigen (HLA) phenotypes of two siblings.26

Although the tissue typing has not shown these patients to have

HLA-B27, in some cases there may be a genetic predisposition,

perhaps associated with the HLAcw6 gene.

FrequencyAcne fulminans is a very rare systemic disease. The patient may

seek initial care from an internist rather a dermatologist. Over the

past several years, its incidence appears to be decreasing, possibly

because of earlier and better treatment of acne.2

AgeAcne fulminans predominantly affects young men aged 13–

22 years with a history of acne. The mean duration of acne before

the onset of AF is 2 years (range 0.5–5).2 The disease in most

patients begins as papulopustular or mild cystic acne and rapidly

becomes AF.

ClinicalThe term AF is appropriate to describe the course of this entity.

Before the sudden onset of the disease, most individuals have mild

to moderate acne. AF occurs usually after institution of tetracy-

cline or isotretinoin therapy.2 It is a unique disease. The primary

features of AF include the following: sudden onset, severe and

often ulcerating acne, fever and polyarthritis, failure to respond to

antibacterial therapy and good response to oral steroids after

4–6 weeks, with the addition of oral isotretinoin.27 At the onset,

the disease resembles acne conglobata with the presence of numer-

ous, highly inflammatory tender and ulcerative nodules covered

with haemorrhagic crusts, distributed mainly on the upper chest,

back and shoulders.28 They are so painful that the patient is unable

to lie on his back. The face is usually less severely involved than

the trunk (Figs 1 and 2). The lesions undergo swift suppurative

degeneration, leaving ulcerations whose base is filled with gelati-

nous, necrotic debris. Open and closed comedones are uncommon

and inconspicuous. In contrast with acne vulgaris, polyporous

Figure 1 Acne fulminans, early, in male adolescent.

Figure 2 Acne fulminans, back, early, in male adolescent.

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Acne fulminans 503

comedones are absent. In contrast with acne conglobata, a wide

spectrum of systemic reactions is seen in patients with AF.

Systemic signs and symptoms are presented in the majority of

patients. The most common systemic signs and symptoms are fati-

gue, malaise, arthralgias, myalgias, fever, anaemia, leucocytosis and

elevated erythrocyte sedimentation rate (ESR). Rheumatoid factor

and anti-nuclear antibody tests have resulted in negative ⁄ non-

reactive findings. Tissue typing has not shown these patients to

have HLA-B27.

Arthralgia and joint swellings may also be present and occur

mainly in large joints such as iliosacral, iliac and knee joints.

Patients may demonstrate a bent-over posture because polyarthri-

tis may make walking painful. Aseptic osteolytic bone lesions and

increased uptake on bone scans have been reported. The predomi-

nant locations for bone lesions are the clavicle, sternum and long

bones of the extremities. The sternum and clavicles are the most

common sites; osteolytic lesions may occur in the hips, ankles and

humerus, as well as the sacroiliac joints. AF tends to smolder for

several months, but the healing is quite slow and often leaves

extensive scarring. It is one of the most scarring acute dermatolog-

ical disorders of young patients. However, there is a subset of

patients with acne of severity comparable with that of AF but with

the absence of systemic involvement.29 This group of AF ‘sine

fulminans’ patients should be delineated, as modification of acne

therapy may be required.

Histologically, the early pustules show an intense infiltrate of

neutrophils and occasional histiocytes with invasion and destruc-

tion of the follicular wall and sebaceous glands. The epidermis

becomes necrotic, secondary to hyalinized thrombotic vessels and

profuse bleeding into the skin. At this stage, the haemorrhagic skin

necrosis is surrounded by a mixed granulocytic and lymphocytic

infiltrate. Some follicles show distension with accumulated kerati-

nized cells (microcomedone formation), but do not reveal any

tendency for comedone formation. A late nodule shows regener-

ated acanthotic epidermis with the dermis containing a dense

mixed cellular infiltrate, vascular hyperplasia and numerous stel-

late fibroblastic cells. Rarely, direct immunofluorescence testing

reveals a linear IgM and fibrin band at the dermo-epidermal junc-

tion and fibrin deposition around the sebaceous glands. In con-

trast to acne conglobata, large non-inflamed secondary cysts and

polyporous comedones are absent. Erythematous neovascular

nodules may also be seen.

Laboratory findingsThere are no consistent laboratory abnormalities in acne fulmin-

ans. Bacterial cultures from blood, joint fluid and skin are usually

sterile. Propionibacterium acnes have been isolated only sporadi-

cally from the bone lesions of patients with AF, but we do not

consider this finding to be of major importance. Anti-staphylo-

coccal and anti-streptococcal antibody levels usually are normal.

Staphylococcus aureus can be discovered occasionally. Cultures for

bacteria from blood and bone usually have been negative,

although a patient has been described with AF in whom culture

from a lytic bone lesion showed P. acnes.30 A patient was docu-

mented as having AF and osteomyelitis with negative bacterial

cultures from the bone.31 However, he had red fluorescence in

the affected bone, which is characteristic for P. acnes. Other labo-

ratory findings in patients with AF may include an increased

ESR, increased levels of C-reactive protein, characteristic leucocy-

tosis sometimes with a leukemoid reaction up to 30 000 ⁄ mm2,

increased percentage of polymorphonuclear leucocytes, elevated

levels of liver enzymes, thrombocytosis, normochromic and

normocytic anaemia. Microscopic haematuria, proteinuria and

other kidney abnormalities are sometimes found. Serum proteins

usually are normal, but may show decreased albumin or increased

a-globulin and c-globulin. Circulating immune complexes have

been found in some patients with both AF and erythema nodo-

sum.9,21 In contrast with acne vulgaris, patients with AF have

shown depressed delayed hypersensitivity to various antigens in

skin tests.32

Acne fulminans if often associated with a leukemoid reaction.33

Two patients had 0.5–1.5% myeloblasts, promyelocytes and myel-

ocytes in the peripheral blood.34 Another man had a milder leuke-

moid reaction, but also developed posterior scleritis of his eyes

and a pyoderma gangrenosum-like eruption on the lower legs.35

Posterior scleritis may be caused by autoimmune mechanism(s);

the primary event in posterior scleritis seems to be vasculitis initi-

ated by deposition of circulating immune complexes in scleral or

episcleral blood vessels and with an association with rheumatoid

arthritis described.36,37 The aetiology of pyoderma gangrenosum is

unclear, but it occurs with systemic diseases such as inflammatory

bowel disease, rheumatoid arthritis and haematological malig-

nancy.38

Imaging studiesBone involvement is common. The occurrence of bone lesions in

AF is rare but well recognized, and often bone biopsies are per-

formed to rule out malignancy or infection. A variety of benign

histological appearances have been reported. Analysis of biopsy

specimens of the bony lesions shows reactive changes only. How-

ever, an infiltrate of neutrophils and mononuclear cells with gran-

ulation tissue may mimic osteomyelitis. The cause of bone lesions

is unknown. No pathogenic bacteria have been found; there is one

patient in whom P. acnes was cultured.30,39 The sites of predilec-

tion include the anterior chest, particularly the sternum and clavi-

cles, but osteolytic lesions have also been reported in the hips,

ankles and humerus. Sacroiliitis has also been described. Initial

lesions are osteolytic; later on, periosteal formation of new bone,

sclerosis and thickening occurs. No erosions or ligamentous ossifi-

cation has been noted. Approximately 50% of patients have

lytic bone lesions demonstrated on radiographs, and 70% of

patients show increased uptake using technetium scintigraphy

(‘hot spots’).40 Destructive lesions resembling osteomyelitis are

demonstrated on radiographs in 25% of patients. Patients with

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504 Zaba et al.

lytic bone lesions may have elevated serum alkaline phosphatase

levels.41

Differential diagnosisThe disease is easily identified because of its prominent systemic

features. Although both diseases have a similar localization, it is

important not to attribute acne fulminan to severe acne conglobata.

AF it is more menacing to health, is resistant to antibiotics, requires

special therapy and is time limited. Acne conglobata is found to

occur more often in women than acne fulminans, develops in older

age and has a more chronic course. The onset of acne conglobata is

less explosive than that of AF. Furthermore, although considered

pathognomonic of acne conglobata, multiple comedones are also

present in a small number of patients with AF.

Acne fulminans can be considered as a part of the spectrum of

the SAPHO syndrome, a clinical condition which describes an

association between musculoskeletal disorders (synovitis, hyperos-

tosis and osteitis) and various dermatological conditions.42,43

Because the clinical similarities among them are obvious, we

believe that these diseases belong to the same auto-immune dis-

ease category. The cause of SAPHO is unclear. It occurs mainly in

children and young adults. The criteria of SAPHO include: (i)

osteoarticular manifestations of palmoplantar pustulosis, severe

acne (fulminans or conglobata) or hidradenitis suppurativa; (ii)

hyperostosis of anterior chest wall, spine, pelvis or limb, with or

without dermatosis; (iii) chronic recurrent multiple osteomyelitis

with or without dermatosis. It has a broad spectrum of clinical

presentation. Skin diseases associated with this syndrome include

palmoplantar pustulosis, hidradenitis suppurativa, severe acne and

various patterns of psoriasis, but the absence of skin lesions does

not exclude the diagnosis of SAPHO. The most frequent sites of

osteoarticular involvement are the anterior chest wall, pelvic girdle,

vertebrae and mandible. Radiologically, patients present usually

sclerosis or osteolysis or a mixture of the two. Systemic manifesta-

tions such as malaise or fever have also been described in SAPHO

syndrome but less frequently.44

TreatmentThe treatment of AF has been challenging. In almost all cases of

AF, systemic steroids have been utilized as the drug of choice

(Table 2). The response has been generally favourable, with a high

relapse rate if the dosage was reduced too quickly. The relapse

usually occurs 2–8 weeks after the acute attack when the corticos-

teroids dosage is reduced or stopped; the relapse manifests as

worsening of arthralgia and sometimes fever, but usually not as

worsening of the cutaneous nodules.2 Pulsed steroid treatment to

control the acute inflammatory phase of the disease may be uti-

lized, with isotretinoin started after the acute inflammatory phase

of the disease has been controlled.45 Systemic corticosteroids (e.g.

0.5–1.0 mg ⁄ kg of prednisolone) are indicated in AF, because they

effectively control the skin lesions, reduce fever and also have a

favourable effect on the musculoskeletal symptoms. Oral steroids

should be started initially to deal with systemic symptoms and

gradually reduced to avoid adverse effects of a prolonged course of

systemic steroids. Symptoms tend to recur when the steroid dose

is lowered or discontinued too quickly. Thus, the required dura-

tion of steroid therapy appears to be as long as 3–5 months to

avoid relapses.

The combination of oral steroids and isotretinoin may be bene-

ficial. Systemic isotretinoin (13-cis-retinoic acid) has been used

successfully in acne fulminans, but paradoxically, may precipitate

acne fulminans.46,47 Accordingly, it is not the initial treatment of

choice.48,49 Isotretinoin has been postulated to increase fragility of

the pilosebaceous duct, leading to massive contact with P. acnes

antigens. Recommended dosage of isotretinoin should not be less

than 0.5 mg ⁄ kg daily, but in some patients an increase to

1.0 mg ⁄ kg or even 2.0 mg ⁄ kg daily may be necessary. Isotretinoin

is started after 4 weeks of corticosteroid treatment. The delay in

starting isotretinoin therapy is necessary. Some recommend very

low doses of isotretinoin (0.1 mg ⁄ kg ⁄ day) initially in patients with

any evidence of crusting to avoid exacerbation. Isotretinoin with a

minimum total dose of 120 mg ⁄ kg is recommended. Duration

of treatment depends upon individual response and usually

Table 2 Recommended treatment for AF

Drug category Comments

Systemic

Corticosteroids (Prednisone) Drug of choice, effectively controlling the skin lesions; prednisone dose: 0.5–1 mg ⁄ kg ⁄ dPO for 6 weeks, decreased as condition improves

Retinoids (Isotretinoin) Beneficial in combination with steroids, initial dose: 0.25 mg ⁄ kg ⁄ d PO, graduallyincreased to 1 mg ⁄ kg ⁄ d; duration of treatment: 3–5 months

Sulfones (Dapsone) Effective in case of AF with erythema nodosum; initial dose: 50 mg ⁄ day, may beincreased to 100 or 150 mg ⁄ day

Azathioprine Used in severe case of AF, in combined therapy with oral steroids

Infliximab Therapeutic option for patients unresponsive to conventional therapies.

Topical

Compresses with urea solution Prevention of accumulation of crusts

Corticosteroids Used in the active phase to diminish the intensity of inflammation

AF, acne fulminans.

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Acne fulminans 505

should not be less than 3–5 months. If required, a repeat course of

isotretinoin (150 mg ⁄ kg) may be used. In most cases, the inflam-

matory reaction can be significantly lessened or even abolished,

but recurrences tend to be more frequent than in acne vulgaris.

Pyogenic granuloma-like vascular proliferations may occur spon-

taneously during isotretinoin treatment. If that happens, the dose

of isotretinoin should be reduced to 0.2 mg ⁄ kg daily.

A US Food and Drug Administration – mandated registry is

now in place for all individuals prescribing, dispensing or taking

isotretinoin. This iPLEDGE registry aims to further decrease the

risk of pregnancy and other unwanted and potentially dangerous

adverse effects during a course of isotretinoin therapy. Sadly, it

often hinders use of this medication.

Patients with AF usually require bed rest and possible hospi-

talization. When admitted to the hospital, the mean duration of

hospital stay is 3–5 weeks.2 The first step in therapy is surgical

debridement, accompanied by frequent warm compresses with

20–40% urea solution to prevent the accumulation of crusts.

Other topical treatments include cleansing with antibacterial

agents and antiseptic lotions. Topical, high-potency corticoster-

oids, applied on all ulcerated nodules twice daily for 7–10 days,

may be beneficial in the active phase to diminish the intensity

of inflammation and ulceration. Pulsed dye laser is one

approach said to be effective for AF and other disorders associ-

ated with hyperplastic granulation tissue. More experience with

it is necessary. The healing may be rapid following pulse dye

laser therapy; complete healing may occur following two laser

treatments.50

Other options can be considered. A 16-year-old boy was

described who developed within a few days AF of devastating

severity.51 Moderate steroid therapy did not give control; he

required both high dosage steroid and azathioprine. A remission

was produced only after many months of additional therapy with

azathioprine. The response to broad-spectrum antibiotic treatment

is poor, but intensive systemic antibiotic therapy is indicated to

combat secondary infection when it occurs. Sulfones, especially

diaminodiphenylsulfone (dapsone) may be of limited value in

AF.6 However, in cases of AF with erythema nodosum, it has been

shown to be effective treatment. The mechanism by which it exerts

an anti-inflammatory action may be related to inhibition of the

myeloperoxidase-H2O2-halide system in polymorphonuclear leu-

cocytes.52 In any case dapsone may be substituted for the retinoid

if it is not acceptable for whatever reason. The initial dose is

50 mg ⁄ day, which can be increased to 100 or 150 mg ⁄ day, rarely

200 mg ⁄ day. The musculoskeletal symptoms and fever generally

respond well to non-steroidal anti-inflammatory drugs. The salicy-

lates have a good effect on the acute myalgia and arthritis. The

most frequently used treatment of musculoskeletal symptoms of

SAPHO has been non-steroidal anti-inflammatory drugs, but may

not be effective. Other therapies, including intra-articular cortico-

steroid, injections, oral corticosteroids, disease-modifying anti-

rheumatic drugs (methotrexate, sulfasalazine and cyclosporine A),

bisphosphonates and infliximab have been administrated with var-

ious results. Serial measurements of the ESR and white blood cell

count provide an objective means of monitoring the therapeutic

response, which may correlate with the clinical course. For the

patients with AF unresponsive to conventional therapies, inflix-

imab might be considered as a treatment option.22 Infliximab, a

chimeric IgG1-kappa monoclonal antibody targeted against

TNF-a, neutralizes TNF-a, leading to a reduction in pro-inflama-

tory cytokines such as IL-1, IL-6 and decreasing cytokines of acute

phase proteins.53 After starting infliximab, ulcerative cutaneous

nodules may begin to noticeably decrease and synovitis, back and

clavicular pain completely resolve.

AF is the most aggressive and destructive form of acne. The

multiple clinical manifestations of AF make the disease sometimes

difficult to recognize. In acne fulminans, the patient’s organism

appears to begin to destroy his own tissues – the skin, the marrow,

the bones and the kidneys. When the treatment is given too late,

patients rapidly develop destructive changes. They suffer the pain

and disability from the skin lesions. Devastating weight losses of

12 kg occurring as quickly as 1.5 kg ⁄ week and dramatic fever as

high as 41 �C has been reported.54 Discontinuation of therapy

may be followed by an exacerbation of the osteoarticular symp-

toms. The relapse usually occurs 2–8 weeks after the acute attack,

when the corticosteroid dosage is reduced or stopped and mani-

fests as worsening of arthralgia and sometimes fever, but usually

not as worsening of the skin lesions. The early institution of

therapy can diminish the degree of scarring and other changes

associated with this potentially disfiguring disease.

PrognosisRecurrent AF is extremely rare. The prognosis for patients effec-

tively treated with corticosteroids and isotretinoin is good. Bone

lesions typically resolve with treatment, but residual radiographic

changes, such as sclerosis and hyperostosis, may remain. Occa-

sional mild musculoskeletal pain in the areas affected by the acute

disease may persist. Scarring and fibrosis may result from this

acute inflammatory process. Sequelae other than scarring are rare.

Relapses can occur, especially when steroid treatment is reduced,

but after 1-year treatment the risk of relapse is small. Promptly

recognizing this disorder will aid in appropriate management.

Appropriate diagnosis of AF allows the patients to avoid multiple

consultations, unnecessary pharmacological treatments and resid-

ual scarring of the skin. In general, AF does not recur when

brought under control.

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