Acne Fulminans 

Updated: Feb 08, 2019
Author: Ryszard Zaba, MD, PhD; Chief Editor: William D James, MD 

Overview

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. See the image below.

Granulomas and crusted acne lesions in acne fulmin Granulomas and crusted acne lesions in acne fulminans. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/doctors/follicular/images/fulmin2.jpg).

Go to Acne Conglobata, Acne Keloidalis Nuchae, Acne Vulgaris, and Acneiform Eruptions for complete information on these topics.

Pathophysiology

Acne fulminans is an uncommon, immunologically induced, systemic disease characterized by aggressive inflammation in which the triggering antigen is believed to be from Cutibacterium acnes (formerly Propionibacterium acnes); it is a severe variant of acne vulgaris. 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 C acnes (formerly P acnes). Acne fulminans could be induced by anabolic steroid use in a male bodybuilder.[4] The trigger for acne induction seemed to be a testosterone therapy in a patient with Marfan syndrome.[5] . The increase in the amount of C acnes (formerly P acnes) or related antigens may trigger the immunologic reaction in some individuals and lead to an occurrence of acne fulminans.[6] In addition to testosterone, isotretinoin may also precipitate acne fulminans, possibly related to highly increased levels of C acnes (formerly P acnes) antigens in the patient's immune system.[7, 8]

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.[9]

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.[10]

Acne fulminans has also been observed in patients with measles infection.[11]

Chronic inflammation in acne fulminans, characteristic to acne lesions, can also be accompanied by angiogenesis. By specific immunostaining for CD34+ endothelial cells, research revealed the presence of blood capillaries around the pilosebaceous follicles, within the inflammatory or pericystic infiltrate.[12]

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.

International

Approximately 150 patients with acne fulminans have been described.[13, 14]

Age

Acne fulminans predominantly affects young males aged 13-22 years with a history of acne.

Prognosis

Recurrent acne fulminans 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.

 

Presentation

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.[15]

Bone pain related to aseptic osteolysis may be present. Acne fulminans with osteolytic changes in the metaphysis of the distal radius was also described.[16] 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.[17]

Patients with acne fulminans and acneiform folliculitis may have chronic aseptic multifocal osteomyelitis.

Physical Examination

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 one joint or several joints, especially the hips, the knees, and the thighs.

 

DDx

Diagnostic Considerations

Also consider the following:

  • Rosacea fulminans

  • Proliferative granulation tissue from use of isotretinoin to treat acne conglobata

  • Acne conglobata: Acne fulminans should be distinguished from acne conglobata because acne fulminans may cause systemic illness, it does not respond to antibiotics, and it requires different therapy.

Differential Diagnoses

 

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

  • Sterile blood culture results

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

Oral Steroids and Isotretinoin

The recommended treatment for acne fulminans is a combination of oral steroids and isotretinoin.[18, 19, 20]

Oral steroids should be started and gradually reduced over 6 weeks to avoid the adverse effects of a prolonged course of systemic steroids. Some authors propose a shift with a 2-week corticosteroid treatment or 4 weeks of steroid treatment before starting isotretinoin.[21]

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.

Suicidal ideation, a concern in seemingly healthy adolescents, should be anticipated in those with cosmetically disturbing skin disorders, such as acne fulminans. Some believe that isotretinoin may exacerbate this tendency.

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 yield a slow response in the resolution of acne and systemic symptoms. However, treatment with broad-spectrum systemic antibiotics including 300 mg clindamycin thrice daily and 750 mg levofloxacin daily in conjunction with 1 mg/kg/day oral prednisolone may be useful in some cases.[14] 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 acne fulminans that is unresponsive to conventional therapies.

Other treatment

Friedlander reported that the pulsed dye laser is effective treatment for acne fulminans–associated granulation tissue.[22]

The addition of diaminodiphenylsulfone was effective for treating the relapse of acne fulminans in a patient with ulcerative colitis who was successfully treated with prednisolone.[23]

In some cases of acne fulminans, treatment with cyclosporine A and prednisolone may be also effective.[24]

A case of acne fulminans was successfully treated with oral prednisone and dapsone.[25]

 

Guidelines

Guidelines Summary

In 2016, the American Academy of Dermatology (AAD) issued new evidence-based guidelines for acne vulgaris treatment of both adolescents and adults. Recommended treatments include topical therapy, antibiotics, isotretinoin, and oral contraceptives.[26] The key recommendations include the following:

  • Benzoyl peroxide or combinations with erythromycin or clindamycin as monotherapy for mild acne; benzoyl peroxide with a topical retinoid or systemic antibiotic therapy for moderate-to-severe acne

  • Topical antibiotics (eg, erythromycin, clindamycin) are not recommended as monotherapy because of the risk of bacterial resistance

  • Topical retinoids as monotherapy in primarily comedonal acne, or in combination with topical or oral antimicrobials for mixed or primarily inflammatory acne

  • Topical adapalene, tretinoin, and benzoyl peroxide can be safely used to treat acne in preadolescent children

  • Topical dapsone 5% gel for inflammatory acne, particularly in adult females

  • Systemic antibiotics are recommended for moderate and severe acne and forms of inflammatory acne that are resistant to topical treatments; doxycycline and minocycline are both more effective than tetracycline

  • Topical therapy with benzoyl peroxide or a retinoid should be used with systemic antibiotics and for maintenance after completion of systemic antibiotic therapy

  • Monotherapy with systemic antibiotics is not recommended

  • Systemic antibiotic use should be limited to the shortest possible duration; to minimize the development of bacterial resistance, reevaluation at 3-4 months

  • Use of oral erythromycin and azithromycin should be limited to those who cannot use the tetracyclines (ie, pregnant women or children aged < 8 y); erythromycin use should be restricted because of its increased risk of bacterial resistance

  • Isotretinoin is recommended for severe acne or moderate acne that does not respond to other therapy; low-dose isotretinoin can be used to effectively treat acne and reduce the frequency and severity of medication-related adverse effects, but intermittent dosing is not recommended; all patients treated with isotretinoin must adhere to the iPLEDGE risk management program; patients should receive routine monitoring of liver function tests, serum cholesterol, and triglycerides at baseline and again until response to treatment is established, but routine monitoring of complete blood count is not recommended; patients should be educated about the potential risks and monitored for any indication of inflammatory bowel disease and depressive symptoms

  • Combined oral contraceptives (COC) containing estrogen are effective for treatment of inflammatory acne in females; physicians should follow the World Health Organization (WHO) recommendations for COC usage eligibility

  • Despite the lack of published data, relying on available evidence, experience, and expert opinion, the guidelines support the use of spironolactone in select women

In 2015, as part of the Choosing Wisely® initiative from the American Board of Internal Medicine Foundation (ABIM), the AAD released recommendations regarding low-value care that cautioned against the routine use of microbiologic testing in the evaluation and management of acne. The AAD concluded that determining the type of bacteria present in acne lesions was unnecessary because it did not alter the management of typical acne presentations.[27]

 

Medication

Medication Summary

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

Corticosteroids

Class Summary

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

Prednisone

Prednisone is a synthetic adrenocortical steroid with predominantly glucocorticoid properties. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reducing capillary permeability. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Prednisolone (Orapred, Pediapred, Millipred)

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body.

Retinoid-like Agents

Class Summary

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

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.

Suicidal ideation, a concern in seemingly healthy adolescents, should be anticipated in those with cosmetically disturbing skin disorders, such as acne fulminans. Some believe that isotretinoin may exacerbate this tendency.

Isotretinoin (Claravis, Amnesteem, Sotret)

Isotretinoin is an aral 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. It decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization.

Tretinoin topical (Avita, Retin-A, Retin-A Micro, Tretin-X)

Tretinoin topical is structurally related to vitamin A. It may be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose therapy may be suitable for selected patients. It may cause skin irritation in some patients. Also, it has been linked to the promotion of angiogenesis; however, it has not demonstrated increased telangiectasias. Tretinoin topical also inhibits microcomedo formation and eliminates lesions. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is available as creams and gels.

Antibiotics, Other

Class Summary

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

Dapsone

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