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Disease Profile

Febrile Ulceronecrotic Mucha-Habermann disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

FUMHD; Ulceronecrotic Mucha-Habermann disease; Variant of Mucha-Habermann disease

Categories

Skin Diseases

Summary

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare and severe form of pityriasis lichenoides et varioliformis acuta (PLEVA).[1][2][3][4][5][6] PLEVA is characterized by skin lesions that ulcerate, breakdown, form open sores, then form a red-brown crust. FUMHD often begins as PLEVA, but then rapidly and suddenly progresses to large, destructive ulcers. There may be fever and extensive, painful loss of skin tissue as well as secondary infection of the ulcers. Diagnosis of FUMHD is confirmed by biopsy of skin lesions. FUMHD occurs more frequently in children, peaking at age 5 to 10.[6] Males tend to be affected more often than females.[2][6] While some cases of FUMHD have resolved without therapy, others have resulted in death. Early diagnosis and prompt treatment may help to reduce morbidity and death.

Symptoms

Initial symptoms of FUMHD include red scaly skin legions (papules) that ulcerate, breakdown, form open sores, then a red-brown crust (i.e., PLEVA).[1][2][3][4][5][6] In FUMHD the legions suddenly progress to large, destructive ulcers and can be associated with extensive, painful loss of skin tissue. The skin lesions can become infected which may cause pus and a putrid odor.[2] The rate of progression from PLEVA to FUMHD varies among reports but may be days to weeks.[2] Some cases go straight to FUMHD rather than progress from PLEVA.[7] FUMHD is often associated with high fever (up to 104°F) that may be persistant or come and go. Other symptoms may include feeling ill, sore throat, congestion, muscle soreness or pain, joint pain, diarrhea, central nervous system symptoms, abdominal pain, enlarged spleen, arthritis, megaloblastic anemia, interstitial pneumonitis (scarring or thickening of the lungs), lymphocytic (viral) myocarditis, and sepsis.[6][1][2][3][7] FUMHD can become life threatening.

Cause

The cause of FUMHD is not known (idiopathic).[1][2] A hypersensitivity to an infectious agent is suggested to be the main cause.[1][2][7][8] Single cases of people with FUMHD and Epstein-Barr virus infection, adenovirus, or cytomegalovirus have been reported, but there has been no consistent finding so far.[2][7] There is some suggestion that FUMHD may be a type of clonal Tcell disorder.[1][2][7][8] “Clonal” means that all the T-cells were derived from the same cell. T cells are a type of white blood cell (lymphocytes). They make up part of the immune system. T cells help the body fight diseases or harmful substances.

Diagnosis

FUMHD is diagnosed based upon the clinical symptoms in the patient, with confirmation by skin biopsy. Skin biopsy findings suggestive of FUMHD are outlined below. Because this information is technical we recommend that you review it with a health care provider:[6] 

  • Epidermis Findings include focal confluent parakeratosis, spongiosis, dyskeratosis, mild to moderate acanthosis, vacuolization of basal layer with necrotic keratino-cytes, occasional intraepidermal vesicles, extensive epidermal necrosis. In advanced disease findings may also include extension of infiltrate into epidermis, invasion of erythrocytes, widespread epidermal necrosis, and nuclear debris in necrotic areas
  • Dermis – Swelling, moderately dense lymphohistiocytic perivascular inflammatory infiltrate usually without atypia, extravasation of lymphocytes and erythrocytes with epidermal invasion, subepidermal vesicles in later lesions, dermal sclerosis in older lesions
  • Vascular changes – Dilation and engorgement of blood vessels in papillary dermis with endothelial proliferation, vascular congestion, occlusion, dermal hemorrhage, and extravasation of erythrocytes
  • Vasculitis – Fibronoid necrosis of vessel walls with leukocytoclassic vasculitis

In the majority of patients, blood tests indicate leukocytosis, anemia, elevated C-reactive protein, and elevated liver enzymes. An association of FUMHD with elevated blood levels of TNF-alpha has also been described.[9]

Treatment

It is important that FUMHD is diagnosed and treated as soon as possible.[1] While a number of treatments have been tried, it is hard to asses the benefit of the therapies because there are so few cases of FUMHD and among reported cases the treatment approach may vary. The case reports describe treatment with systemic steroids, methotrexate, antibiotics, dapsone, cyclosporine, psoralen and ultraviolet A (PUVA), ultraviolet B (UVB), unspecified ultraviolet receptor, acyclovir, immunoglobulins, and 4,4-diaminodiphenylsulphone (DDS). Again the efficacy of these therapies are not known.[1][2][3][6][7][8][9] 

Acyclovir was prescribed in cases where varicella was initially suspected. None of these cases turned out to be associated with herpes simplex or varicella-zoster virus infection. The benefit of acyclovir therapy in people with FUMHD is questionable.[2]

Systemic steroids have been commonly utilized among reported cases (27 of 40 cases), with only one report of a positive effect.[7] Methotrexate has been used in 15 patients. It induced rapid remissions and was successful in cases that did not respond to other therapies. Still four patients died despite methotrexate theapy. It is possible this was due to its late institution.[7]

Debridement and skin grafting was successful in one case, but the patient was left with considerable scaring.[1]

In advanced disease, therapy is also aimed at stabilizing the patient. Intensive care treatment of infection and maintenance of the patient’s general condition is vital.[1][7] The state of these patients is similar to what is seen in patients with severe burns. Thus, patients with FUMHD may benefit from the same supportive services that burn victims receive.[9]

Treatment with tumor necrosis factor (TNF)-alpha inhibitors (such as infliximab and etanercept) has been suggested as a first-line option in the management of FUMHD because elevated levels of serum TNF-alpha have been reported in this disease[7][10] However, further studies may be required to establish this approach to treatment.

More detailed information about treatment options for FUMHD can be accessed through the DermNet NZ web site.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The British Association of Dermatologists provides an informational leaflet on pityriasis lichenoides. Click on the British Association of Dermatologists link to view this leaflet.
      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
      • The medical website TheDoctorsDoctor also provides information on PLEVA and FUMHD. Click on the link above to view the information page.

        In-Depth Information

        • Medscape Reference provides information on PLEVA which includes information on FUMHD. You may need to register to view the article, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Febrile Ulceronecrotic Mucha-Habermann disease. Click on the link to view a sample search on this topic.

          Resources for Kids

            Selected Full-Text Journal Articles

              References

              1. Aytekin S, Balci G, Duzgun OY. Febrile ulceronecrotic Mucha-Habermann disease: a case report and a review of the literature. Dermatol Online J. December 1 2005; 11(3):31. https://www.ncbi.nlm.nih.gov/pubmed/16409927.
              2. Yang CC, Lee JY, Chen W. Febrile ulceronecrotic Mucha-Habermann disease with extensive skin necrosis in intertriginous areas. Eur J Dermatol. September-October 2003; 13(5):493-6. https://www.ncbi.nlm.nih.gov/pubmed/14693498.
              3. Miyamoto T, Takayama N, Kitada S, Hagari Y, Mihara M. Febrile ulceronecrotic Mucha-Habermann disease: a case report and a review of the literature. J Clin Pathol. October 2003; 56(10):795-797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770083/.
              4. Hoghton MA, Ellis JP, Hayes MJ. Febrile ulceronecrotic Mucha Habermann disease: a fatality. J R Soc Med. August 1989; 82(8):500-501. Febrile ulceronecrotic Mucha Habermann disease: a fatality.
              5. Miller ML. Miscellaneous Conditions Associated with Arthritis. In: Kliegman. Nelson Textbook of Pediatrics, 18th ed. Philadelphia, PA: Saunders; 2007;
              6. Bowers S, Warshaw EM. Pityriasis lichenoides and its subtypes. J Am Acad Dermatol. October 2006; 55(4):557-72. https://www.ncbi.nlm.nih.gov/pubmed/17010734.
              7. Sotiriou E, Patsatsi A, Tsorova C, Lazaridou E, Sotiriadis D. Febrile ulceronecrotic Mucha-Habermann disease: a case report and review of the literature. Acta Derm Venereol. 2008; 88(4):350-5. https://www.ncbi.nlm.nih.gov/pubmed/18709304.
              8. Oliveira L, Rocha M, Patriota G, Cunha G, Paiva G, Souza A, Fauth A, de Moura C, Cruz C. Febrile Ulceronecrotic Mucha Habermann Disease: Case Report of a Dark-Skinned Patient. Case Rep Dermatol. 2013 Jan-Apr; 5(1):4-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573822/.
              9. Harenberg P, Hrabowski M, Ryssel H, Gazyakan E, Germann G, Engel H, Reichenberger M. Case Report Febrile Ulceronecrotic Mucha-Habermann Disease. Eplasty. 2010 Jul 16; 10:e53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905190/.
              10. Tsianakas A, Hoeger PH. Transition of pityriasis lichenoides et varioliformis acuta to febrile ulceronecrotic Mucha-Habermann disease is associated with elevated serum tumour necrosis factor-alpha. Br J Dermatol. April 2005; 152(4):794-9. https://www.ncbi.nlm.nih.gov/pubmed/15840118.
              11. Cozzio A, Hafner J, Kempf W, Häffner A, Palmedo G, Michaelis S, Gilliet M, Zimmermann D, Burg G. Febrile ulceronecrotic Mucha-Habermann disease with clonality: A cutaneous T-cell lymphoma entity?. Am Acd Dermatol. December 2004; 51(6):1014-7. https://www.ncbi.nlm.nih.gov/pubmed/15583604.

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