Malakoplakia 

Updated: Apr 16, 2019
Author: Amira M Elbendary, MBBCh, MSc; Chief Editor: William D James, MD 

Overview

Background

Malakoplakia is a rare granulomatous disease of infectious etiology that involves the skin and other organs.[1, 2]  The name is derived from the Greek malakos (soft) and plakos (plaque), describing its usual clinical presentation as friable yellow soft plaques.

It was first described by von Hansemann in 1901 and in 1902 by Michaelis and Gutmann.[3]

Malakoplakia is most frequently reported to occur in the genitourinary system. The first case of malakoplakia reported to occur outside the genitourinary system was in 1958.[4] Since then, various organs have been reported to be affected.

Cutaneous malakoplakia is rare and was first reported in 1972 by Leclerc and Bernier.[5]

Malakoplakia is usually reported in the setting of immunocompromise, although rare reports in immunocompetent individuals have been documented.

Malakoplakia presents clinically with a wide spectrum of findings, and the criterion standard for diagnosis is pathological examination.

Pathophysiology

Malakoplakia is believed to result from the inadequate killing of bacteria by macrophages or monocytes that exhibit defective phagolysosomal activity. Partially digested bacteria accumulate in monocytes or macrophages and lead to the deposition of calcium and iron on residual bacterial glycolipid. The presence of the resulting basophilic inclusion structure, the Michaelis-Gutmann body, is considered pathognomonic for malakoplakia. See the image below.

Michaelis-Gutmann body in a patient with malakopla Michaelis-Gutmann body in a patient with malakoplakia.

Studies have suggested that a decreased intracellular cyclic guanosine monophosphate (cGMP) level may interfere with adequate microtubular function and lysosomal activity, leading to an incomplete elimination of bacteria from macrophages and monocytes.

The incidence of malakoplakia in immunocompromised states, including post organ transplantation, diabetes mellitus, AIDS, malignancy, and immunosuppressive therapy, suggests that a disturbed function of T lymphocytes may play a role in the pathogenesis of malakoplakia in patients in states of immunocompromise.[3]

Etiology

The most common organism isolated was Escherichia coli. Other organisms isolated include Klebsiella and Proteus species. Although E coli is the most common gram-negative bacterium isolated, other enteric bacteria may be found on culture. Staphylococcus aureus,Pseudomonas aeruginosa, and Rhodococcus equi may also be cultured.[6]

Defective macrophage killing of these bacteria leads to malakoplakia. Defective macrophage killing results in an accumulation of bacterial degradation products and a granulomatous reaction, which clinically manifests as the formation of a papule, a plaque, or an ulceration.

Risk factors for the development of malakoplakia include the following[7, 8, 9, 10] :

  • Immunosuppressive therapy after organ transplantation

  • Malignant lymphoma on chemotherapy

  • Myelodysplastic syndrome

  • Post radiotherapy

  • Diabetes mellitus

  • Alcoholism

  • Rheumatoid arthritis

  • Dermatomyositis

  • Lupus vulgaris

  • Carcinoma of the breast post mastectomy

  • Concomitant urinary tract infection

  • Prolonged therapy with systemic corticosteroids

Other rare associations that have been reported include papillary urothelial carcinoma[11] and abdominal malakoplakia following blunt trauma to the abdomen.[12]

Epidemiology

Frequency

The total number of patients with malakoplakia is fewer than 500. Most patients have genitourinary tract disease, although involvement of the gastrointestinal tract and other visceral organs has been described. Cutaneous malakoplakia is rare, with fewer than 60 cases reported in the literature. Because this disease is often diagnosed after biopsy of nondescript lesions, the true incidence is most likely higher.

Race

Cutaneous malakoplakia is more commonly reported in whites (39%) than in African Americans (19%) or Asians (12%), although the patient's ethnic group is often not specified in case reports.

Sex

Cutaneous malakoplakia occurs with a male-to-female ratio of 2.3:1.

Age

Cutaneous malakoplakia presents in patients with a broad age range. The median age at the time of presentation is 53 years. Occurrence of the disease is associated more with the presence of an immunocompromised state affecting monocyte and macrophage function than with age.

Prognosis

Malakoplakia most often occurs in patients who are immunocompromised. Often, malakoplakia is resistant to treatment, with a mean duration of the skin lesions of 3-6 months. Malakoplakia shows a variable course and, in rare cases, can be fatal.[4] Mortality in patients with malakoplakia is most often due to an underlying condition.

Cutaneous lesions usually follow a benign clinical course. The cure rate following surgery with or without antibiotics is about 80%.[13, 14]

Significant morbidity relates to the chronicity of the condition, which can resist local and systemic therapy. Draining sinuses, persistence of disfiguring skin lesions, and involvement of visceral organs constitute significant morbidity in patients with malakoplakia.

Patient Education

Instruct patients who are immunosuppressed, who have undergone organ transplantation, or who are receiving systemic corticosteroids to notify the physician if they notice a fleshy mass that is growing slowly and ulcerating.

 

Presentation

History

Patients typically present with a history of immunosuppression due to renal transplantation,[15] diabetes mellitus, or lymphoma or a history of receiving long-term therapy with systemic corticosteroids.[16, 17]

Close to one quarter of patients present with internal organ involvement, most commonly in the retroperitoneal area, the kidney, the bladder, or the colon. Symptoms reflect the organ system involved, but patients can often present with draining sinuses originating from deeper organ involvement.

Malakoplakia rarely presents in patients with HIV infection[18] and AIDS,[19] which may be because of the preservation of monocytic antimicrobial function in these patients.

Malakoplakia can mimic colonic,[20, 21, 22, 23, 24] gastric,[25] pancreatic,[26] oropharyngeal,[27, 28] or genital tract carcinoma.[29, 30] Involvement of the bone[31] and the lungs has also caused diagnostic difficulty. Malakoplakia can present with renal failure[32, 33] or a pyelonephritislike picture.[34]

Physical Examination

Malakoplakia lesions may present as erythematous papules, subcutaneous nodules, draining abscesses, ulcers, nonhealing surgical wounds, indurated plaque, or draining fistulas.[35, 36, 37, 38]

Malakoplakia was also reported masquerading as pyoderma gangrenosum, presenting as a nonhealing malleolar ulcer for 2 years.[39] The most common site affected in the reported cases was perianal (19%). Other affected sites included the abdomen, face, neck, and vulva.[40] In one study, perianal and inguinal skin, vulva, and scrotum were affected in 41% of patients with cutaneous malakoplakia, followed by abdominal wall, thorax, and head and neck at 20% and by extremities and axilla at 10%.[41]  

The most common presentation in reported cases of cutaneous malakoplakia is nodules (23%), with about one quarter of these lesions complicated by abscess or ulcer formation.

Rarely, malakoplakia involves more than one anatomical site in the same patient.[42]

Duration varies from weeks to months and, rarely, years.

Complications

Complications include local disfigurement and organ dysfunction with visceral involvement.

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

Culture the draining sinuses for aerobic, anaerobic, fungal, and mycobacterial pathogens.

Imaging Studies

Positron emission tomography scanning has been used to diagnose malakoplakia in 2 cases of renal disease. Intense uptake of fluorodeoxyglucose was noted in the kidney.[43, 44]

MRI of a patient with renal malakoplakia has shown multiple nodules with low signal on T1-weighted, T2-weighted, and early and late postgadolinium images.[45]

Because the appearance of testicular malakoplakia on sonography overlaps with that of testicular neoplasm and infection, it should be considered when making a differential diagnosis of a diffuse testicular abnormality.[46]

Procedures

Perform a biopsy of the skin lesion. Tissue processing follows by using routine hematoxylin and eosin stain, periodic acid–Schiff stain, von Kossa stain for calcium, and Perls Prussian blue stain for iron.

Malakoplakia may lead to an overestimation of the stage of an underlying gastrointestinal malignancy. Careful consideration and evaluation of biopsy material is required to exclude this condition and correctly stage the patient to direct therapy for the underlying cancer.

Other Tests

A minimally invasive technique using image-guided aspiration and cytomorphological analysis was reported to help diagnose a case of pancreatic malakoplakia and avoid possibly unnecessary surgeries for suspected tumor.[42]

Histologic Findings

Sheets of ovoid histiocytes with fine eosinophilic cytoplasmic granules (von Hansemann cells) are seen on routine staining. Histiocytes with 5- to 15-mm basophilic inclusions with concentric laminations (Michaelis-Gutmann bodies) are diagnostic. Michaelis-Gutmann bodies demonstrate positive results using periodic acid–Schiff stain and are diastase resistant. They stain with von Kossa stain for calcium and Perls Prussian blue stain for iron.

Electron microscopy results show that Michaelis-Gutmann bodies consist of lysosomes filled with partially digested bacteria. Gram stain may demonstrate gram-negative bacteria. Immunohistochemical studies demonstrate positive results for CD68 antibodies, lysosomes, and α -chymotrypsin. Immunostaining with polyclonal anti– Mycobacterium bovis antibody may demonstrate organisms in patients with malakoplakia.

See the images below.

Cutaneous malakoplakia. Cutaneous malakoplakia.
Michaelis-Gutmann body in a patient with malakopla Michaelis-Gutmann body in a patient with malakoplakia.
 

Treatment

Medical Care

Generally, cutaneous malakoplakia is treated in an outpatient setting. Therapy with antibiotics that concentrate in macrophages (eg, quinolone, trimethoprim-sulfamethoxazole) is associated with a high cure rate.[47] Antibiotic therapy directed against E coli in combination with surgery provides the best chance of cure.

Bethanechol, a choline agonist, has been used in combination with antibiotics and surgery. Bethanechol may correct the decreased cGMP levels that are believed to interfere with complete bacterial killing.[48]

Ascorbic acid has been used to increase the cGMP and cyclic adenosine monophosphate (cAMP) levels in monocytes, which may represent an effective strategy for therapy. An insufficient number of patients have been treated with ascorbic acid to determine its overall effect.[48]

Discontinuation of immunosuppressive drug therapy is usually needed to effectively treat malakoplakia.[49]  However, it was reported that sustained antimicrobial therapy together with reduction of immunosuppression may be appropriate for treating malakoplakia with reduction of the risk of poor graft survival in patients taking immunosuppression following renal transplantation.

Surgical Care

Excision of skin lesions and drainage of abscesses are fundamental to diagnosis and treatment. Surgery combined with antibiotic therapy should be directed against E coli or other organisms recovered on culture.

Consultations

Consultation with a dermatologist and/or an infectious disease specialist may be necessary.

Prevention

Patients should notify the physician if they develop a chronic skin lesion. Immunosuppressive agents should be used with caution in patients with a prior history of malakoplakia.

Long-Term Monitoring

Patients should receive follow-up observation until the skin lesions resolve clinically. Patients may require a prolonged course of antibiotic therapy.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antibiotics

Class Summary

Antimicrobials directed against gram-negative bacteria, especially E coli, are used to treat patients with malakoplakia. In addition, antibiotics that concentrate in macrophages are used. Quinolone antibiotics (eg, ciprofloxacin) and sulfonamides (eg, trimethoprim-sulfamethoxazole) are indicated. Bethanechol and ascorbic acid have also been used in the treatment of patients with malakoplakia.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone that has activity against Pseudomonas and Streptococcus species, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but has no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 days (7-14 days typical) after signs and symptoms have disappeared.

Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Trimethoprim and sulfamethoxazole inhibit bacterial growth by inhibiting synthesis of dihydrofolic acid. The antibacterial activity of this combination of drugs includes common urinary tract pathogens except P aeruginosa.

Cholinergic agents

Class Summary

These agents increase the contractility of the bladder.

Bethanechol hydrochloride (Duvoid, Myotonachol, Urabeth, Urecholine)

Bethanechol hydrochloride is used for selective stimulation of the bladder to produce contractions to initiate micturition and to empty the bladder. It has been found to be most useful in patients who have bladder hypocontractility, provided they have functional and coordinated sphincters. Bethanechol hydrochloride is rarely used because of the difficulty in timing the effect and because of gastrointestinal tract stimulation.

Vitamins

Class Summary

Vitamins with the ability to induce collagen fibril synthesis are used.

Ascorbic acid (C-Crystals, Ascorbicap, Cevi-Bid, Vita-C)

Ascorbic acid is used for collagen synthesis and tissue repair.