eMedicine Specialties > Dermatology > Diseases of the Adnexa

Acne Fulminans

Ryszard Zaba, MD, PhD, Director, Department of Dermatology, Professor, Department of Dermatology and Venereology, Poznan University School of Medical Sciences, Poland
Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Updated: Mar 12, 2009

Introduction

Background

Acne fulminans (AF), also known as acne maligna, was originally described as acute febrile ulcerative acne conglobata (AC). In 1958, at a meeting of the Detroit Dermatological Society, Burns and Colville presented a 16-year-old white boy with acute febrile disease and acne conglobata. Many similar cases have been reported since then.¹ The primary features of this disease include sudden onset, severe and often ulcerating acne, fever, polyarthritis,² and failure to respond to antibacterial therapy; the response to debridement in combination with steroid therapy is good. It can be the dermatologic manifestation of the synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome.³ Acne fulminans is a syndrome of fulminant, necrotizing acne associated with bone lesions, constitutional symptoms, and laboratory abnormalities.

Other acne-related eMedicine articles include Acne Conglobata, Acne Keloidalis Nuchae, Acne Vulgaris, and Acneiform Eruptions.

Pathophysiology

Acne fulminansis an uncommon, immunologically induced, systemic disease in which the triggering antigen is believed to be from Propionibacterium acnes. Some authors note that elevated blood levels of testosterone may play an important role in the pathogenesis of acne fulminans. High levels of testosterone and anabolic steroids cause an increase in sebum excretion and in the population density of P acnes. The trigger for acne induction seemed to be a testosterone therapy in a patient with Marfan syndrome.⁴ The increase in the amount of P acnes or related antigens may trigger the immunologic reaction in some individuals and lead to an occurrence of acne fulminans.⁵ In addition to testosterone, isotretinoin may also precipitate acne fulminans, possibly related to highly increased levels of P acnes antigens in the patient's immune system.⁶

Another theory postulates that acne fulminans may be an autoimmune complex disease because circulating immune complexes have been demonstrated in some patients with acne fulminans. Immunologically, the reaction is a type III or IV hypersensitivity reaction.

Genetic factors may play an important role in some patients; 4 sets of identical twins who developed an identical pattern of acne fulminans have been documented.⁷

Acne may be the only clinical sign of androgen excess in men, and one report is available about a boy with acne fulminans and androgen excess due to late-onset congenital adrenal hyperplasia.⁸

Frequency

United States

Acne fulminans is a rare disease. Over the past several years, fewer cases of this disease have occurred, possibly because of earlier and better treatment of acne.

Age

Acne fulminans predominantly affects young males with a history of acne.

Clinical

History

The primary features of this disease include the following:
- Sudden onset
- Severe and often ulcerating acne
- Fever and polyarthritis
- Failure to respond to antibacterial therapy
- Good response to oral steroid therapy, after 4-6 weeks, the addition of oral isotretinoin
Acne fulminans predominantly affects young males with a history of acne.
Painful splenomegaly and erythema nodosum may be present.⁹
Bone pain related to aseptic osteolysis may be present. Gordon et al report a case of a 13-year-old boy with severe acne and multiple osteolytic bone lesions who presented to pediatric oncologists; the patient avoided unnecessary painful diagnostic procedures when it was recognized he had acne fulminans.¹⁰
Patients with acne fulminans and acneiform folliculitis may have chronic aseptic multifocal osteomyelitis.

Physical

Acne fulminans (similar to acne conglobata) demonstrates numerous inflammatory nodules on the trunk. In acne fulminans, the large nodules tend to become painful ulcers with overhanging borders surrounding exudative necrotic plaques that become confluent; however, polyporous comedones and noninflammatory cysts are not evident (as seen in acne conglobata). Erythematous neovascular nodules may also be seen.
Acne fulminans is a systemic disease. Patients may demonstrate a bent-over posture because polyarthritis may make walking painful.
Inflammatory arthralgia may affect 1 joint or several joints, especially the hips, the knees, and the thighs.

Causes

See Pathophysiology.

Differential Diagnoses

Acne Conglobata
Acne Vulgaris
Acneiform Eruptions
Pyoderma Gangrenosum

Workup

Laboratory Studies

Findings in patients with acne fulminans include the following:
- Leukocytosis (characteristic finding)
- Increased percentage of polymorphonuclear leukocytes
- Anemia
- Leukemic-type reaction
- Elevated erythrocyte sedimentation rate
- Circulating immune complexes
- Proteinuria
Blood cultures are universally sterile.

Imaging Studies

Bone involvement is common.
- Approximately 50% of patients have lytic bone lesions demonstrated on radiographs, and 70% of patients show increased uptake using technetium scintillography ("hot spots").
- Destructive lesions resembling osteomyelitis are demonstrated on radiographs in 25% of patients.
- Multifocal osteolytic cysts may be evident as tender bones and can be detected as hot spots by technetium scintillography.

Histologic Findings

Analysis of biopsy specimens of the bony lesions shows reactive changes only.

Treatment

Medical Care

The recommended treatment for acne fulminans is a combination of oral steroids and isotretinoin.^11,12,13

Oral steroids should be started and gradually reduced over 6 weeks to avoid adverse effects of a prolonged course of systemic steroids.
Isotretinoin should be started at 4 weeks, initially at 0.25 mg/kg daily and gradually increased to achieve complete clearance. Isotretinoin with a minimum total dose of 120 mg/kg is recommended. Relapses are rare. If required, a repeat course of isotretinoin (150 mg/kg) may be used.
Some authors suggest treating patients with spontaneous development of acne fulminans with oral steroids and supplemental intralesional therapy.
The response to broad-spectrum antibiotic treatment is poor. Oral antibiotics are responsible for a slow response in the resolution of acne and systemic symptoms. The combination of oral isotretinoin and systemic steroids is better than the combination of oral isotretinoin and antibiotics.
Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, also may be a treatment option for patients with AF that is unresponsive to conventional therapies.

Surgical Care

Friedlander reported that the pulsed dye laser is effective treatment for acne fulminans – associated granulation tissue.¹⁴

Medication

Begin treatment with oral prednisone 1 mg/kg/d and taper over 6 weeks. By the fourth week, initiate isotretinoin at 0.25 mg/kg/d. If isotretinoin cannot be used, dapsone may be substituted for the retinoid, beginning at 50 mg/d and increasing to 100-150 mg/d.

Corticosteroids

These agents have profound and varied metabolic effects. They possess anti-inflammatory and immunosuppressive properties.

Prednisone (Delta-Cortef, Econopred)

Synthetic adrenocortical steroid with predominantly glucocorticoid properties. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Dosing

Adult

0.5-1 mg/kg/d PO for 6 wk; taper as condition improves
Single morning dose is safer for long-term use, but divided doses have greater anti-inflammatory effects

Pediatric

0.14-2 mg/kg/d initial PO divided tid/qid (4-60 mg/m²/d)

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral, fungal, connective tissue, and tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI tract disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur

Retinoids

Vitamin A derivatives have many roles. They encourage cellular differentiation, are antiproliferative, and serve as immunomodulators.

Isotretinoin (Accutane)

Oral agent that treats serious dermatologic conditions. Isotretinoin is the synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to beta-carotene. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Dosing

Adult

Initial: 0.25 mg/kg/d PO; increase gradually (usually 1 mg/kg/d) for 20 wk or a total dose of 120-150 mg/kg

Pediatric

Administer as in adults

Interactions

Toxicity may occur with beta carotene coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasionally exaggerated healing response of acne lesions (ie, excessive granulation with crusting) may occur; patients with diabetes may experience problems controlling blood glucose levels while on isotretinoin; avoid exposure to UV light or sunlight until tolerance is achieved; discontinue if rectal bleeding, abdominal pain, or severe diarrhea occurs; mood swings or depression may occur; caution in history of depression.

Tretinoin (Avita, Retin-A, Retin-A Micro)

Structurally related to vitamin A. May be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose therapy may be suitable for selected patients.
May cause skin irritation in some patients. Also, has been linked to promotion of angiogenesis; however, has not demonstrated increased telangiectasias.
Also inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Available also as 0.01% and 0.025% gels.

Dosing

Adult

Begin with lowest concentration of tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops

Pediatric

<12 years: Not established
>12 years: Apply as in adults

Interactions

Toxicity may occur with vitamin A coadministration; toxicity increased when coadministered with sulfur, benzoyl peroxide, resorcinol, or any product with strong drying effects; phototoxicity increased when coadministered with tetracyclines, fluoroquinolones, or thiazides

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with excessive sunlight exposure; burning, stinging, peeling, pruritus, or erythema has been reported at site of application; caution with eczema (may cause severe irritation); avoid contact with mucous membranes, mouth, and angles of nose

Sulfone antibiotics

These agents may inhibit bacterial growth by preventing the formation of folic acid.

Dapsone (Avlosulfon)

Bactericidal and bacteriostatic against Mycobacteria species; mechanism of action is similar to that of sulfonamides in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Anti-inflammatory mechanism of action may involve suppression of neutrophil function by inhibition of the halide-myeloperoxidase system. Excretion is primarily in urine; half-life is 28 h.

Dosing

Adult

50-150 mg PO qd

Pediatric

Not established

Interactions

May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine); monitor for agranulocytosis during second and third mo of therapy; probenecid increases toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of increase in renal clearance, levels may decrease significantly when administered concurrently with rifampin; avoid use with zalcitabine because of increased risk of peripheral neuropathy (additive effects)

Contraindications

Documented hypersensitivity; G-6-PD deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform weekly blood counts (first mo), then WBC counts monthly (6 mo), then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis occurs; caution in patients with methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light

Follow-up

Prognosis

Recurrent AF is extremely rare.
Bone lesions typically resolve with treatment, but residual radiographic changes, such as sclerosis and hyperostosis, may remain.
Scarring and fibrosis may result from this acute inflammatory process.

Patient Education

For excellent patient education resources, visit eMedicine's Skin, Hair, and Nails Center and Teen Health Center. Also, see eMedicine's patient education articles Acne.

Miscellaneous

Medicolegal Pitfalls

Suicidal ideation, a concern in seemingly healthy adolescents, should be anticipated in those with cosmetically disturbing skin disorders, such as AF. Some believe that isotretinoin may exacerbate this tendency.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

References

Burns RE, Colville JM. Acne conglobata with septicemia. Arch Dermatol. 1959;79:361-3.
Windom RE, Sanford JP, Ziff M. Acne conglobata and arthritis. Arthritis Rheum. Dec 1961;4:632-5. [Medline].
Iqbal M, Kolodney MS. Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated with infliximab. J Am Acad Dermatol. May 2005;52(5 Suppl 1):S118-20. [Medline].
Wollina U, Gesina H, Koch A, Kostler E. Case reports: acne fulminans in Marfan syndrome. J Drugs Dermatol. Jul-Aug 2005;4(4):501-5. [Medline].
Heydenreich G. Testosterone and anabolic steroids and acne fulminans. Arch Dermatol. Apr 1989;125(4):571-2. [Medline].
Kalbarczyk K, Ciupinska M. Complications during treatment with Roaccutane, acne fulminans 2001. Dermatol Klin (Wroclaw). 2001;3 (Suppl 1):130.
Palatsi R, Oikarinen A. Hormonal analysis and delayed hypersensitivity reactions in identical twins with severe acne. Acta Derm Venereol. 1979;59(2):157-60. [Medline].
Placzek M, Degitz K, Schmidt H, Plewig G. Acne fulminans in late-onset congenital adrenal hyperplasia. Lancet. Aug 28 1999;354(9180):739-40. [Medline].
Williamson DM, Cunliffe WJ, Gatecliff M, Scott DG. Acute ulcerative acne conglobata (acne fulminans) with erythema nodosum. Clin Exp Dermatol. Dec 1977;2(4):351-4. [Medline].
Gordon PM, Farr PM, Milligan A. Acne fulminans and bone lesions may present to other specialties. Pediatr Dermatol. Nov-Dec 1997;14(6):446-8. [Medline].
Allison MA, Dunn CL, Person DA. Acne fulminans treated with isotretinoin and "pulse" corticosteroids. Pediatr Dermatol. Jan-Feb 1997;14(1):39-42. [Medline].
Leyden JJ. The role of isotretinoin in the treatment of acne: personal observations. J Am Acad Dermatol. Aug 1998;39(2 Pt 3):S45-9. [Medline].
Seukeran DC, Cunliffe WJ. The treatment of acne fulminans: a review of 25 cases. Br J Dermatol. Aug 1999;141(2):307-9. [Medline].
Friedlander SF. Effective treatment of acne fulminans-associated granulation tissue with the pulsed dye laser. Pediatr Dermatol. Sep-Oct 1998;15(5):396-8. [Medline].
Champion RH, Burton JL, Burns DA, Breathnach SM, eds. Rook/Wilkinson/Ebling Textbook of Dermatology. 6^th ed. Oxford, England: Blackwell Science; 1998:1967-79.
Cunliffe WJ, Gollnick H. Acne fulminans. In: Cunliffe WJ, Gollnick H. Acne. Diagnosis and Management. London, England: Martin Dunitz Ltd; 2001:84-6.
Jansen T, Plewig G. Acne fulminans. Int J Dermatol. Apr 1998;37(4):254-7. [Medline].
Jansen T, Romiti R, Plewig G. Acute severe acne in a female patient (acne fulminans?). Br J Dermatol. Nov 1999;141(5):945-7. [Medline].
Thomson KF, Cunliffe WJ. Acne fulminans 'sine fulminans'. Clin Exp Dermatol. Jun 2000;25(4):299-301. [Medline].

Keywords

acne fulminans, acute febrile ulcerative conglobata acne with polyarthritis, acute febrile ulcerative conglobata acne with leukemoid reaction, acne maligna, acute ulcerative acne conglobata

Contributor Information and Disclosures

Author

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Alexa F Boer Kimball, MD, MPH, Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital and Brigham and Women's Hospital
Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire Consulting

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

Further Reading

eMedicine Specialties > Dermatology > Diseases of the Adnexa

Acne Fulminans

Introduction

Background

Pathophysiology

Frequency

United States

Age

Clinical

History

Physical

Causes

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Imaging Studies

Histologic Findings

Treatment

Medical Care

Surgical Care

Medication

Corticosteroids

Prednisone (Delta-Cortef, Econopred)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Retinoids

Isotretinoin (Accutane)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Tretinoin (Avita, Retin-A, Retin-A Micro)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Sulfone antibiotics

Dapsone (Avlosulfon)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Follow-up

Prognosis

Patient Education

Miscellaneous

Medicolegal Pitfalls

References

Keywords

Contributor Information and Disclosures

Author

Coauthor(s)

Medical Editor

Pharmacy Editor

Managing Editor

CME Editor

Chief Editor